C. H. WADDINGTON

How Animals Develop

A SHORT ACCOUNT OF THE SCIENCE OF EMBRYOLOGY

Revised Edition
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HOW ANIMALS DEVELOP

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HOW

ANIMALS DEVELOP

C. H. Waddington, M. A.

Fellow of Chris fs College^ Cambridge

Strangeways Research Laboratory^ Laboratory oj

Experimental Zoology, Cambridge

HARPER TORCHBOOKS

The Science Library j
Harper & Brothers ▼
New York

HOW ANIMALS DEVELOP

New material Copyright @ 1962
by C. H. Waddington
Printed in the United States of America
This book was originally published in 1935 by
Allen lb- Unwin, Ltd., London and is reprinted
by arrangement. A new last section, "The Ac-
tivity of Genes in Development" has been writ-
ten by Dr. Waddington.
First HARPER TORCHBOOK edition published 1962

FOREWORD

In this book, I have tried to write an account of
embryology suitable for the intelligent layman and
the elementary students I have been conscious of
two main difficulties in this task. Firstly, embryos
are complicated and unfamiliar things, so that one
has to describe their structure before one can
discuss the problems they present. I have attempted
to avoid too much description by concentrating on
the early stages of development, which are as a
matter of fact the most important from a general
theoretical point of view, and can be described
fairly shortly, since the embryos have not yet had
time to develop any great complexity of form. The
second difficulty arises because embryology is so
interesting. The development of the structures by
which living things carry out the activities of life
must clearly raise many of the most fundamental
problems about the nature of life itself. But most of
the answers to these problems are still obscure. In
order to show the directions in which people's
thoughts are being led by the recent progress of
embryology, I have put forward some of my own
views, perhaps without sufficient warning that they
represent probabilities rather than certainties. If I
had attempted to give all the possible interpretations
of the facts the book would have become unwieldy
and confusing, but it was impossible to shirk a
discussion of the problems. I believe the ideas which

HOW ANIMALS DEVELOP

I have put forward are those most generally held
by people who are working at embryology at the
present day, but to-morrow we may discover some
new fact which will force us to modify them. When
one is brought face to face with the most fundamental
questions about living things, one cannot expect to
obtain complete answers in the comparatively short
time during which biology has been actively studied.

C. H. W.

CAMBRIDGE
1935

ACKNOWLEDGMENTS

For permission to reproduce illustrations acknow-
ledgment is made to the Cambridge University Press
(Engelbach, Endocrinology ; Behrens and Barr, Endo-
crinology; Huxley and de Beer, Experimental Embryo-
logy), Messrs. Longmans, Green & Co. (Quain,
Anatomy), Messrs. Macmillan & Co. (MacBride,
Invertebrate Embryology), the Railway Gazette (photo-
graph of Whitemoor Marshalling Yard, L.N.E.R..),
and to my own publishers (Durken, Experimental
Analysis of Development; Stockard, Physical Basis of
Personality) .

CONTENTS

CIIAPflR PAGE

FOREWORD

I. INTRODUCTION I3

The development of animal organization — The
similarity of all young embryos — The three
fundamental layers

II. THE BEGINNING OF DEVELOPMENT 26

Egg and sperm — Fertilization, heredity, virgin
birth — Development begins

III. MOVEMENTS AND FOLDINGS 4O

Formation of the three layers in sea-urchins —
Frogs and newts — Lampreys — Birds — Mammals

IV. THE "organization CENTRE*' 61

The technique of micro-surgery — The focus
around which the embryo is integrated — Birds
— Mammals — Sea-urchins — Insects

V. THE ADDITION OF DETAILS 78

Secondary organization centres — Special fac-
tories making special parts — Mosaic eggs —
Different ways of* building up similar struc-
tures— Larvae

VI. THE DEVELOPMENT OF PATTERN 93

How the organizer works — Particular causes
and the general pattern — Regeneration

VII. THE FINAL ADJUSTMENTS 102

How embryos are fed — Growth — The influence
of function — The nervous system and develop-
ment— Hormones — Sex — The activity of genes
in development

INDEX 135

LIST OF ILLUSTRATIONS

FIG. PAGE

1. EGG-CELL AND SPERM-CELL 26

2. ORDINARY CELL-DIVISION 2Q

3. CELL-DIVISION IN THE FORMATION

OF THE GERM-CELLS 29

4. FORMATION OF GERM-CELLS 3I

5. INHERITANCE OF SHORT FINGERS 33

6. THE EFFECT OF YOLK ON CLEAVAGE 36

7. SPEMANN's TYING-UP EXPERIMENT 38

8. BLASTULA AND GASTRULA OF SEA-

URCHIN 42
9a. DEVELOPMENT OF THE NEWT's EGG

facing page 42

gb. OPERATING ON A NEWT's EMBRYO

facing page 43

10. VOGT's dye EXPERIMENT ON THE

newt's EMBRYO 45

11. MAPS OF THE NEWT AND LAMPREY

EGGS 46

12. CULTURE VESSEL FOR EMBRYOS 5I

13. THE ORIGIN OF THE MESODERM IN

THE CHICK 52

14. MAP OF THE CHICK EMBRYO 54

15. DEVELOPMENT OF THE RABBIT 57

HOW ANIMALS DEVELOP

FIG. PAGE

i6. spemann's exchange experlment

IN the newt 65

17. an organizer graft in the newt 68

18. AN organizer graft IN THE CHICK

facing page 70

19. A GRAFTING EXPERIMENT IN THE

SEA-URCHIN 74

20. DEVELOPMENT OF THE DRAGON-FLY 76

21. DEVELOPMENT OF THE EYE IN

VERTEBRATES 79

22. SELF-DIFFERENTIATION OF THE LEG

BONES OF A CHICK facing page ^2

23. DEVELOPMENT OF THE EYE IN THE

OCTOPUS 89

24. CATERPILLAR 91

25. WHITEMOOR MARSHALLING YARD,

L.N.E.R. facing page 93

26. DIFFERENT TYPES OF PLACENTA IO7

27. GROWTH OF MAN AND GORILLA IIO

28. VEGETARIAN AND CARNIVOROUS TAD-

POLES 112

29. EFFECTS OF THE PITUITARY GLAND

facing page 114

30. FACES OF MEN AND DOGS facing page 1 1 ^

HOW ANIMALS DEVELOP

CHAPTER I
INTRODUCTION

The Development of Animal Organization

Living animals are constantly on the move. It is
one of the most characteristic things about them.
Often we can see them running about, breathing,
catching food and eating it, and so on. If we look
closer we find that an animal is made up of different
organs, and in all of them there is something going
on all the time. On an even smaller scale, the organs
are built out of cells, little lumps of living matter,
each containing a special kernel or nucleus. And each
cell is always full of activity. In plants the living
jelly streams slowly about from one side of the cell
to the other: in animal cells we cannot usually see
any movement, but nevertheless there are incessant
chemical actions and reactions. The cell absorbs
oxygen and other substances from outside, performs
many complicated chemical operations with them,
and pours out again into its surroundings the by-
products for which it has no use.

In a living organism these changes are not isolated
but are adjusted to one another so that the right
operations are carried out to produce the right
quantities of the various products. It is because

14 HOW ANIMALS DEVELOP

we are so impressed at the way in which all the
separate processes work together harmoniously that
we call animals "organisms." The processes which
keep an animal alive have to be quite as highly
organized as the operations in the most complicated
mass-production factory. If there is a "secret of life,"
it is here we must look for it, among the causes
which bring about the arrangement of innumerable
separate processes into a single harmonious living
organism.

When a numerous and varied set of processes is
to be organized it is obviously convenient, and
often absolutely necessary, to separate the different
jobs among different pieces of apparatus, each of
which specializes in carrying out one particular
function. Thus a motor-car has a separate apparatus
— the carburettor — ^to vaporize the fuel, another
apparatus — the dynamo — ^to provide electric power,
still another — the sparking plug — to make a spark,
and so on. We find the same sort of plan adopted
in all animals which attain more than a very minute
size. For instance, every living creature has to
arrange to absorb oxygen from its surroundings and
to transport it in the right quantities to the cells in
the body which need it. We find that there are
special organs for absorbing it, lungs in animals
which breathe air, gills in animals which absorb the
oxygen dissolved in water; special organs, the
blood-vessels, for transporting the oxygen all through
the body after it has been absorbed and dissolved
in the blood ; a heart to pump the blood along ; and

INTRODUCTION 1 5

many other organs to regulate the speed at which
the lungs work and the blood flows. Without this
rather complicated machinery, the organization of
the oxygen supply would be inconceivable. The de-
velopment of a set of specialized structures is the first
step in the business of building up a living organism.

To say that an animal is an organism means in
fact two things : firstly, that it is a system made up
of separate parts, and secondly, that in order to
describe fully how any one part works one has to
refer either to the whole system or to the other parts.
Thus it is impossible to describe fully a thighbone
without referring to the fact that it is part of a leg,
and that one end fits on to a pelvis and the other on
to a shinbone. The relation with the other parts of the
organism is indeed so close that if an anatomist finds
a new fossil bone he can often reconstruct, in general
outline, the whole unknown animal to which it belongs.

There are two possible ways of investigating the
organization of an animal. Firstly, we can study in
the adult how the organism works as a going
concern: we can find out what functions are per-
formed by each separate organ; we can discover
how the communications between the organs are
maintained by the blood and nerves; and we can
study the results of removing one or more organs.
But all the processes which can be investigated in
this way will be proceeding within the framework
provided by the fundamental spatial pattern in
which the parts of the animal are arranged, since in
the adult this pattern is more or less fixed. We can

1 6 HOW ANIMALS DEVELOP

move large lumps of the pattern about, but we cannot
discover what caused the pattern in the first place.

But there is a second line of attack. We can
actually watch how the parts of a living organism
come into being and fit together. Nearly all organisms
start life as fertilized eggs, though a few grow out
as buds from other organisms. Fertilized eggs are
very simple-looking, often apparently quite homo-
geneous lumps of living matter. They consist of a
watery jelly, the protoplasm, which contains a variable
amount of food-matter or yolk, and which also
encloses a little bag of special material which is the
kernel or nucleus. As we shall see, the jelly-like
protoplasm is not really as simple as it looks. But it
is at any rate much simpler than the adult animal,
which consists of very large numbers of cells, of
several different kinds, arranged in various ways to
build up the different organs. During the increase
in complexity as the egg develops into the adult the
spatial pattern of the animal arises. In the early
stages it is fluid and unfixed; we can describe its
gradual unfolding, make experiments which alter it,
study its genesis and causation.

The study of development, or embryology, because
it offers the possibility of finding out how the most
fundamental characteristic of living things, their
organization, comes into being, has always been of
compelling interest to everyone who has been con-
cerned with the position of living things in the
general philosophical scheme. Nearly all biological
philosophers, from Aristotle to the present day, have

INTRODUCTION 1 *]

been embryologists. Aristotle, in fact, founded the
science. He opened hens' eggs after they had been
incubated for various lengths of time, and described
what he saw. For centuries, embryology remained
a purely descriptive science. The changes which
embryos go through as they develop are so many
and complicated that it took an enormous amount
of careful and painstaking work simply to describe
them. Scientists have always asked why the changes
occur; but only in the last fifty years or so have
they been able to perform experiments to try to find
out ; before that they could only guess, and, naturally
enough, their guesses were usually wide of the mark.
Even now we know very little about the causes
which underlie embryonic development, but this is
the most important and interesting part of the
subject, and in this book I shall lay more emphasis
on the tentative beginnings of our knowledge about
the causes of development than on the description
of the changes which occur.

One very important fact has been discovered and
will be described later on in the book. It has been
found that at a rather late stage the organization
of an embryo is comparatively loose and the various
parts are to a large extent independent of one another
and of the whole embryo as regards the way they
develop. 1 At an earlier stage, on the other hand, it

^ Though not, of course, as regards the way they work : in
this stage a lung can develop quite independently of the heart,
but it cannot function to aerate the blood without the help of
a heart.

1 8 HOW ANIMALS DEVELOP

has been found that the way any part develops is
controlled in such a way that all the material which
is available is worked up into one whole animal;
and further, it has been shown that this integrating
control is exerted by one particular part of the
embryo. At this early stage, then, the embryo is
very highly organized, because the way any part
behaves in development cannot be described without
referring to this special controlling part. The con-
trolling part is therefore called the Organizer. I shall
devote quite a considerable amount of space to a
consideration of the organizers which have already
been discovered, and the way in which they throw
light on the other facts which have emerged in the
study of development.

The main interest of embryology at present is
theoretical, in the way discussed above. But there
are a very large number of important practical
questions which we may hope to be able to tackle
later, when the science has been worked out more
fully. For instance, why do most of the higher
animals, including man, lose the power of regenera-
tion so early in life, long before they are born? It
would be very convenient if we could regenerate an
amputated leg. Again, why do some cells start to
form an unorganized cancerous growth which the
animal cannot control, escaping from the agents
which keep the parts of an organism together as one
whole? How can we affect the production of twins
from one ^gg'^ The answers to these questions are
not, I think, right over the horizon of our present

INTRODUCTION 1 9

view in embryology, but are quite near in front
of us.

The Similarity of all young Embryos

The study of embryology was given a great fillip by
the publication, and general acceptance among
scientists, of Darwin's theory of evolution. It had
already been found that the most general features
of an animal's organization, those by which it was
classified as a vertebrate, say, were formed early in
its development, and only later there arose the more
specialized characteristics by which it could be
classified as a bird or a mammal, while still later it
would develop the particular features of a fowl or
a duck. This means that in the very earliest stages
in development all embryos only show those charac-
ters which are common to all animals. They must
therefore look more or less alike. We have only to
describe the early stages and on the basis of their
common pattern we can make a general scheme
into which all embryos fit, and can classify the ways
in which they gradually diverge from each other.

Soon after the publication of Darwin's Origin of
Species, Haeckel put forward a general theory about
these early similarities. He supposed that each
animal, as it develops from the o^gg to the adult,
passes through a series of stages, each of which is
similar to one of its ancestors in the course of the
evolutionary history of the species to which it belongs.
The series is more or less in the right order, so that
the stage representing the first generalized ancestral

20 HOW ANIMALS DEVELOP

vertebrate occurs before the stages representing the
various groups which gradually evolved out of the
original vertebrate stock. This hypothesis brings
under one head a large number of very odd facts.
For instance, a young mammalian embryo, such as
a young human embryo about four or five weeks
old, is provided with gill slits and blood-vessels which
flow along them. These are like the organs found in
fish, where the blood flows through the gills and
absorbs oxygen from the water, but they can be of no
possible use to a mammalian embryo, which at this
stage is deriving its oxygen from the blood-stream
of its mother. HaeckePs theory, that such organs are
** hang-overs" from the time when the ancestors of
mammals were fish, still provides the most con-
venient way of describing this whole class of
phenomena. But we have slightly modified the
expression of Haeckel's theory. Many details of
embryonic development are better described as
reflections not of adult ancestors, as Haeckel thought,
but rather of the embryonic stages of those ancestors.
The mammalian embryo has gill slits, not like the
gills its ancestors had when they were adult, but
like the gill slits they had when they were embryos.
With this modification, Haeckel's hypothesis, the
so-called "biogenetic law" or recapitulation hypo-
thesis, is still one of the foundations of our system of
descriptive embryology.

But even so, there are very many features of
development to which the law does not apply. Many
embryonic characteristics do not represent any

INTRODUCTION 2 1

ancestral conditions, and not by any means all its
ancestors are recapitulated in an animal's develop-
ment. Embryos which live in special situations, like
the bird embryo developing inside its shell, or the
mammal in the womb of its mother, form peculiar
organs suited to their particular conditions, and
these often have little to do with any ancestral
forms. We shall meet other examples of Haeckel's
law later on, when discussing different types of
larvae.

Haeckel's law is not strictly an explanation
of anything. When a human embryo is developing,
its remote fish-like ancestors are long dead and
rotted to mud on the sea floor, and cannot possibly
be the effective agents which cause the human to
form embryonic gill slits. In order to give a satis-
factory account of the direct causes of development,
one must be able to show how the development is
dependent on factors which are actually present in
the fertilized egg or its immediate surroundings.
What Haeckel did was to find a good way of
describing the plethora of odd facts which had been
accumulated. We ought to be able to find a reason
why so many facts fit into Haeckel's generalization.
Actually we still have not found any satisfactory
reason, although we can suggest various processes
which may be involved. Thus if there is to be an
evolutionary change from fish into men, it is
obviously easier, or so a man would think, to stick
to the old plan of development until it is no longer
a help and simply must be altered. The same thing

22 HOW ANIMALS DEVELOP

happens in human inventions. When motor-cars
were first made, the engineers did not think the
whole problem out from the beginning and produce
a stream-lined model with the engine over the back
wheels where the power is required: they seem to
have been exhausted by thinking out the engine,
and simply attached it to the current form of horse-
carriage in front where the horse had been. We can
call this a sort of "habit reason" ; men inventing,
and embryos developing, tend to do what their
fathers did if they can, because it is easier.

There may be other and more important reasons
for imitating an old pattern. It may act as a guide.
For instance, if one is going to make a cast-iron pot,
one first models it in clay, as though iron had not
yet been discovered; from the clay pot a mould is
made into which the molten iron can be poured.
Here the ''ancestral" clay pot provides what may
be called a formative stimulus for the "more highly
evolved" iron pot. Perhaps this sort of explanation
applies to ancestral characters which appear in
embryos only for a short time, eventually dis-
appearing entirely.

The Three Fundamental Layers

It follows from HaeckePs biogenetic law that young
embryos must look much alike, since they should
show only the characters which are common to all
types of animals. This deduction from the law is
actually true. Even before Hacckel definitely formu-
lated his law quite a large number of different kinds

INTRODUCTION 23

of animals had been investigated, and it had been
found that in their early development they all passed
through the same two stages. These stages are called
the blastula and gastrula, and presumably represent
the ancestors from which all animals have been
derived. The original form of Haeckel's law suggests
that these ancestors looked like blastulae or gastrulae
when they were adult, but no animals of this kind
have survived till the present day. In fact, if we
adopt the modification of Haeckel's law which was
advanced above, there is no need to suppose that
adult blastulae and gastrulae have ever existed; we
need only assume that the original ancestral organ-
isms from which all animals have been evolved
passed through these two stages in their development.
There is quite a large amount of variation in the
shapes assumed by the blastulae and gastrulae of
different animals, but we can imagine ideal forms
from which all the others can be derived by minor
modifications. The ideal blastula consists of a hollow
ball of cells, the walls of which are only cell-thick.
The hollow inside is called the blastula cavity, or
blastocoel. The ideal gastrula is also a hollow ball,
but differs from the blastula in two ways; the ball
is punctured, and the walls are thicker and consist
first of two layers of cells and later of three. The
hollow inside, together with the innermost layer
which lines it, is the primitive gut, and communicates
with the outside through the hole which punctures
the ball. This hole is called the blastopore, because
when it becomes visible as a little pore on the blastula

2 4 HOW ANIMALS DEVELOP

surface it often provides the first visible indication
that the blastula is changing into a gastrula. The
three layers out of which the gastrula is made are
named from the Greek words for skin, and for
outside, inside, and middle; thus the outer layer is
the ectoderm, the innermost layer the endoderrriy and
the layer between them mesoderm.

The ectoderm, endoderm, and mesoderm are the
three fundamental parts out of which an animal is
built. We might almost say that they correspond to
the three major parts of a motor-car. The ectoderm
develops into the skin, the sense organs, and the
brain and nervous system; analogous to the body-
work, the lamps, and the controls. The mesoderm
forms the skeleton, muscles, and heart, or the chassis
and engine. Finally the endoderm corresponds to
the fuel system, and develops into the stomach and
intestines and all the apparatus for absorbing food
(i.e. fuel) ; this has to be much more complicated
in an animal than the fuel system is in a car, because
animals cannot get their nourishment poured into
them in a form in which it can be used at once, as
petrol is poured into the tank ; it is as if a car had
to carry round with it a whole refinery for turning
crude oil into motor spirit. These three layers are
called the Germ-Layers, and, when it was first pro-
pounded, the idea that they could be found in some
form or other in all animals stimulated scientists to
investigate as many different kinds of embryos as
possible to see if the hypothesis was true. Most of
this work was completed by the beginning of this

INTRODUCTION 25

century, and it provided a broad basis of information
on which all our present-day knowledge of em-
bryology has been built up. On the whole, it was
found that the three germ-layers could be fairly
easily recognized in most animals, but there are a
few difficult cases, and in some very primitive
animals only the ectoderm and endoderm are present
and there is no mesoderm. The particular impor-
tance of the idea of the germ-layers from our point
of view is that it is the beginning of an analysis of
the pattern in which the embryo is organized. The
formation of the three germ-layers is usually the first
structural change which the embryo achieves, and
almost immediately after this the main organs are
formed. The process by which the blastula turns
into the gastrula is known as gastrulation^ and a great
deal of the discussion later on in the book as to how
development is brought about will be concerned
with this period of gastrulation when the main
structure is blocked out.

CHAPTER II
THE BEGINNING OF DEVELOPMENT

Egg and Sperm

The history of a developing animal really begins
when the egg-cell becomes fertilized by uniting with
a sperm-cell, but before this can happen there must
occur a very important series of processes by which

NUCLEUS

•... HEAD

O* \ T. CENTREPIECE

TAIL

a b

Fig. I. — Diagram of an Egg-cell (a) and a Sperm-cell (b). The
sperm is more highly magnified; in Man the egg is 0-2 mm. in
diameter and the sperm about 0-05 mm. or i /500th inch long,

including the tail

these cells are elaborated. Egg- and sperm-cells are
known collectively as germ-cells, and like other cells
they consist of a mass of living matter or protoplasm,
containing a nucleus. But in the details of their
structure (Fig. i) they are very specialized and
unlike normal cells, as might be expected from the
extraordinary things they have to do. The egg-cell
is usually rather large as cells go, since it has to

THE BEGINNING OF DEVELOPMENT 27

contain food material for the embryo to use before
it develops a digestive apparatus. This food material
is stored as grains of yolk, which are scattered
through the cytoplasm, that is to say, all the proto-
plasm outside the nucleus. As it is fairly heavy, the
yolk collects at the bottom of the ^gg, which is
therefore stratified, with a yolk-laden vegetative pole
below and a non-yolky animal pole at the top. The
nucleus usually lies near the top, in the clear
protoplasm of the animal pole. Non-yolky eggs are
often not very much bigger than other cells; the
human tgg, for instance, is about o • 2 mm. or a
hundredth of an inch in diameter. But when there
is much yolk, the egg-cell may be swollen to an
enormous size. The ''yolks" of birds' eggs are single
cells, the biggest known, with only a tiny little patch
of cytoplasm nearly hidden in the huge mass of
yolk. The sperm-cell is still more highly specialized.
It consists of three parts : the head which contains
the nucleus, the centre-piece, and a long tail which
beats to and fro and drives the sperm actively about
through the fluid in which it exists. Sperm-cells are
very small, containing no yolk and hardly any cyto-
plasm, and their light construction enables them to
move about comparatively rapidly. A human sperm
can travel at the rate of about an inch in three minutes.
Eggs, on the contrary, are rarely able to move.

The most important part in the elaboration of the
germ-cells is the preparation of the nucleus, and this
process is essentially the same both in the eggs and
in the sperm. For most of the time the nucleus of

28 HOW ANIMALS DEVELOP

an ordinary cell consists of a bag made of the nuclear
membrane filled with rather liquid protoplasm. When
the cell is about to divide into two the nuclear
membrane disappears, and out of the liquid contents
there are built up a number of little solid lumps,
which if the cell is killed can be stained very deeply
with many dyes, and are therefore called chromosomes^
from the Greek words for "colour" and "body."
Different chromosomes are often different in shape,
so that they can be recognized, and it is very
important to notice that they always occur in pairs,
so that each cell has two of each kind. The number
and shape of the chromosomes in the cell is fixed for
any particular species, but is different in different
species ; some have as few as four, others up to one or
two hundred. But as the chromosomes are always in
pairs of similar ones the number must always be even.
When the chromosomes become visible at the begin-
ning of an ordinary cell-division, each one is already
split longitudinally into two half-chromosomes lying
side by side. As the cell divides, these two halves
separate from each other, and one half goes into each
of the two cells which are formed. When the division is
over they count as whole chromosomes, and gradually
disappear into a normal fluid nucleus (Fig. 2).

The cell-division which results in the formation of
the germ-cells seems superficially very different from
the ordinary divisions, but it has recently been
realized that the whole difference follows from one
single slight alteration in the way the division begins.
The difference is this: that when the chromosomes

THE BEGINNING OF DEVELOPMENT

29

Fig. 2. Fig. 3.

Fig. 2, — Diagram of ordinary cell-division, (a) The chromo-
somes appear, already double, in the nucleus, (b) The cell
divides and one-half of each double chromosome goes to
each daughter cell

Fig. 3. — Diagram of cell-division during the formation of
the germ-cells, {a) The chromosomes apjjear single in the
nucleus, (a') The two chromosomes of each kind lie side
by side, {b) The cell divides and one chromosome from each
pair goes into each daughter cell

30 HOW ANIMALS DEVELOP

appear before the germ-cell division they are not
split longitudinally (Fig. 3). They do not seem to
be able to proceed with the division until they have
arranged themselves into double bodies, to corre-
spond with the two half-chromosomes lying side by
side which are found in ordinary division. They get
into a doubled condition in the only way which is
open to them ; that is, by the two whole chromosomes
belonging to a pair joining up with each other and
lying side by side. If there are six chromosomes,
two A's, two B's, and two C's, for example, the two
A's always join up, and so do the two B*s and the
two C's. The chromosomes are now a series of
paired bodies, which are just like the split chromo-
somes of an ordinary cell-division to look at, except
that there are only half as many of them. They go
on behaving just like the split chromosomes described
above ; that is to say, the two partners in each paired
body, which have only just come together, now
proceed to separate, one partner going into each of
the two daughter-cells. This means that the two
daughter-cells have only got half the normal number
of chromosomes and are an exception to the general
rule in that they have only one chromosome of each
kind. That is one of the most important character-
istics of the germ-cells. The ordinary body-cells,
which all have two of each kind of chromosome, are
said to have the diploid number, and the germ-cells,
which have only one of each kind, are said to have
the haploid number. The process which has just been
described is spoken of as the reduction division of the

THE BEGINNING OF DEVELOPMENT

31

chromosomes because it involves the reduction of
their number to half.

The daughter-cells of the reduction division are
not the actual germ-cells, but each one has to go

O

MATURATION PERIOD

REDUCTION DIVISION .

O

REDUCTION
DIVISION

0

d o

Qo 06 6606

PERIOD OP
DIFFERENTIATION

a b

Fig. 4. — Diagram of the formation of the germ-cells, (a) The ^%%.
(b) The sperm. The egg mother-cell is built up and furnished with
yolk during the maturation period, and then undergoes two divisions,
giving four cells of which three are very small and die. The sperm
mother-cell divides twice and all four resulting cells are transformed
into sperms during the period of differentiation.

through one ordinary division before it is ready,
giving a total of four germ-cells from each cell which
started the reduction process. Actually, in the forma-
tion of the eggs three of these four degenerate and
never function as eggs, while the remaining one has to
undergo a period of ripening when it is supplied with
the yolk which it will require. This ripening usually
happens in the middle of the reduction division^
which therefore takes a very long time (Fig. 4).

32 HOW ANIMALS DEVELOP

Fertilization^ Heredity^ Virgin Birth

At the end of all this preparation the germ-cells are
ready to carry out the complicated process of
developing into an adult, and are finally ready for
fertilization. Fertilization really consists of two
processes, the activation of the ^gg by the sperm
and the union of the o^gg and sperm nuclei. It is
easy to see the importance of the second process ; it
restores the diploid number of the chromosomes by
adding the haploid number in the sperm to the
haploid number in the ^gg. A properly balanced set
of chromosomes is essential for the development of
the animal since they contain the hereditary factors.
An example will show how the influence of the
hereditary factors can be detected. Men are some-
times born with short fingers, each with only two
joints instead of three, because of some abnormality
in the development of the fingers. The character is
hereditary. For instance, we find short-fingered men
who have married normal wives and all of whose
children have short fingers. If two children born of
such parents then marry, on an average one-quarter
of their children will be normal and three-quarters
short-fingered. These facts are due to the presence
of a hereditary factor or gene for short fingers lying
in a chromosome. The short-finger gene is an
abnormal form of the gene which causes the fingers
to develop in the ordinary way, and is derived from
it by a sudden and as yet inexplicable change called
a mutation. The original short-fingered fathers have

THE BEGINNING OF DEVELOPMENT 33

two similar chromosomes, each with a gene for
short fingers, and each of their germ-cells contains
one chromosome with the short-fingered gene. When
such a sperm fertilizes a normal egg containing a
gene for ordinary fingers, the children have one of
each kind of gene. In this particular case it is the
short-fingered gene which affects the development:
it is therefore said to be dominant over the ordinary

PARENTS Ss St

GERM-CELLS

CHILDREN ISS 2 St Iss

Fig. 5.— Diagram of the inheritance of short fingers. S is the factor
for short fingers and s that for ordinary fingers. The lines show
the ways in which the factors may come together in fertilization.

gene, which is recessive to it. When the germ-cells
are formed in the children of such a marriage, the
two genes, lying in the two similar chromosomes,
are separated at the reduction division, and the
germ-cells have half of them one normal gene and
half of them one short-finger gene. If two such
children marry (Fig. 5), it is pure chance which
genes come together in the fertilized eggs, so that
in half the eggs a normal gene will meet a short-
finger, giving short-fingered adults, in a quarter of
the eggs there will be two short-finger genes, giving
more short-fingered adults, and in the last quarter

34 HOW ANIMALS DEVELOP

there will be two normal genes giving normal adults.
Hereditary factors of this kind were discovered by
Mendel in the middle of the last century, and he
also gave rules for the way in which they are
inherited. Chromosomes had not been described at
that time, and it is only about thirty years since it
was realized that the hereditary factors actually lie
on the chromosomes and that Mendel's laws are
perfectly well explained by the behaviour of the
chromosomes which we have described above. The
theories propounded by Mendel are collectively
known as '^ MendelisnC and are part of the science
of genetics^ or the study of heredity.

It is clear, then, that the chromosomes, or the
genes within them, play a leading role in develop-
ment, and we shall have to discuss later (see
Chapter vii) how they do it. But we can say now
that an ^gg can develop without a full double set
of chromosomes ; it can develop quite well, so long
as it has got a half or haploid set. Anything less than
this is fatal, and so usually is anything between a
half and a whole set because of its lack of balance.
Professor Dalcq in Brussels is investigating the
development of frogs' eggs with less than the haploid
number of chromosomes, and is finding out just
when and how the embryos fail.

The other process in fertilization is the activation
of the tgg. We know very little about how this
happens. What it does is to cause the ^gg to start
dividing and developing. Now the same change can
be brought about by other things which are not the

THE BEGINNING OF DEVELOPMENT 35

sperm, and we then get a "virgin birth," or partheno-
genesis as it is called in science. The most various
and unexpected agents may be effective. It is some-
times only necessary to prick the tgg with a sharp
needle, or to put it into very weak acid ; some marine
eggs may be caused to begin developing if the
salt-concentration of the water is altered. In all cases
the procedures give rather variable results, and we
have very little idea why they give any results at all.
But the eggs treated in this way, since they have a
haploid set of chromosomes, can go on developing
quite normally. The adult which arises is smaller
than normal, and its cells are smaller than normal,
since they adjust their volume to that of the half-sized
nuclei. Some eggs normally develop without being
fertilized by sperm, i.e. parthenogenetically. This
happens, for instance, to many of the eggs of bees,
and these parthenogenetic eggs give rise to drones
or males, which have only the haploid number of
chromosomes. In some species such animals can
produce sperm without performing another reduc-
tion division, but usually they are sterile. In other
cases the ^gg starts developing parthenogenetically,
and then succeeds in doubling its chromosome
number, so that the diploid condition is restored.

Development Begins

The first steps in the development of the tgg are
always the same; the egg divides up into smaller
and smaller cells without growing at all, till there
is a mass of little cells in place of the large single

36

HOW ANIMALS DEVELOP

egg-cell. This process is known as the cleavage of the
tgg. The details vary according to the amount of
yolk which the tgg contains. Eggs with very little yolk
cleave into equal parts ; those with rather more yolk

NO
YOLK

SOME
YOLK

MUCH
YOLK

EGG

CLEAVAGE STAGE

BLASTULA

Fig. 6. — Diagrammatic sections of eggs, cleavage stages and blastulae
with various amounts of yolk

cleave into small cells at the top or animal pole
and larger cells at the bottom where the yolk is
collected. Eggs with a great deal of yolk, such as
birds' eggs, do not cleave throughout their whole
mass : only the patch of non-yolky cytoplasm cleaves,
forming a plate of little cells swimming on the
surface of the main mass of uncleaved yolk. Such

THE BEGINNING OF DEVELOPMENT 37

eggs are said to have partial or discoidal cleavage, as
opposed to the total cleavage of the less yolky types.
The total cleavage, as we have said, may be equal
or unequal (Fig. 6), and further, it may be quite at
random, forming a confused mass of cells ; but often,
particularly in the "total unequal" cleavages, it
follows regular rules, so that the resulting cells are
arranged in a definite pattern. An example of this,
in the sea-urchin's o^gg, is described later (see p. 73).
The cleavage cuts up the large egg-cell into
smaller cells, each of which, we can imagine, is
more completely under the control of its nucleus
than the unwieldy egg could be. It would be easy
to suppose, and at one time it was supposed, that
the nuclei divide unequally during the cleavage, so
that the nuclei are unlike each other, and cause the
cells in which they lie to develop in different ways
into the various organs of the adult. But as a matter
of fact this supposition is quite wrong : the cleavage
nuclei are all alike. A very neat proof of this has
been given by Spemann (Fig. 7). He tied a hair
round a fertilized newt's tgg^ pinching it into a
dumb-bell shape, so that the nucleus lay at one end
and the other end had no nucleus. The end with
the nucleus cleaved, while the other end did not.
After several cleavages the knot was loosened and a
nucleus, whichever happened by chance to lie
nearest, allowed to pass through the bridge between
the two ends. The second end now started to cleave,
and it developed, not into any special part of the
embryo depending on which nucleus it got, but into

38 HOW ANIMALS DEVELOP

a whole embryo. In fact, the egg developed into
twins. This experiment proved that any cleavage
nucleus can develop into a whole embryo, and that

Fig. 7. — Spemann's tying-up experiment. (From Spemann.) The

upper half has cleaved several times and a nucleus has just passed

down into the bottom iialf, which has cleaved once

they are therefore all the same. Changes probably
go on in the nucleus in later stages of development ;
but they are not important in the cleavage period,
and do not determine how the parts of the embryo
will develop. Even in later stages of development
the genes still seem to be present in the nucleus and

THE BEGINNING OF DEVELOPMENT 39

Still active, since it is sometimes found that a gene
has mutated, or changed into one of its other forms,
in a body-cell of a late embryo, and it is then still
capable of affecting the few daughter-cells which
subsequently arise from it.

Spemann*s experiment in which he made artificial
twins raises the whole question of whether half an
egg will always develop as well as a whole egg, and
if so why an tgg usually develops into only one adult
and not two. But it will be more convenient to
postpone discussing this problem (see Chapter vi)
till we have dealt with the next period of develop-
ment, the gastrulation period, in which the main
outhne of the embryo is formed. When the cleavages
finish the egg is a blastula, a hollow ball of cells.
The blastula-cavity appears quite early in eggs with
a total cleavage, since the daughter-cells remain
mure or less spherical and leave a space in the
middle, just as tennis balls would if they were packed
together. This space grows until it is much larger
than the individual cells, which continually decrease
in size as the cleavages proceed. In large yolky eggs
with a discoidal cleavage the hollowness is not so
obvious, but the disc of cells Ufts slightly away from
the mass of yolk and leaves a narrow space which
corresponds to the blastula-cavity (Fig. 6). The
next chapter describes how this hollow ball of cells
is converted into a three-layered gastrula.

CHAPTER III
MOVEMENTS AND FOLDINGS

In the blastula stage, the three fundamental layers
— the ectoderm, endoderm, and mesoderm — are all
simply different parts of the surface wall of a hollow
ball. If they are to arrive at their right places, with
the endoderm inside the ectoderm and the mesoderm
in between, a series of foldings has to be carried out.
There are several different methods of folding, as
we shall see, but they all lead to this same result.
We might compare the development of embryos to
making toys by folding up pieces of paper ; but with
embryos, whatever the final shape, the folding always
starts by producing a three-layered gastrula, just as
if we are making toys we often start by making a
hat shape, and then go on to further foldings which
turn it into a boat or a frog or whatever it may be.
We shall have to describe some of the different
ways in which the gastrula is produced, both because
this is the most important process in the develop-
ment of the embryo, and also as an example of how
the same process appears in a slightly different form
in different animals. In some embryos it is actually
a folding which occurs, but in others the layers
move into their right places by a streaming move-
ment, sweeping across the surface and around the
inside of the gastrula like glaciers moving down a
mountain side. As a general rule, the lower thiC

MOVEMENTS AND FOLDINGS 4 1

animal is in the evolutionary scale, the simpler its
gastrulation. The animals which are described here
are selected partly because they have been particu-
larly well investigated, and partly as typical repre-
sentatives of this series of gradually increasing
complexity. Thus we shall begin with the simple
gastrulation of the sea-urchins and go on to primitive
vertebrates like newts and lampreys, working up to
more highly evolved groups of vertebrates like birds,
and finally to mammals, which have developed a
special container, the womb, in which development
takes place.

The Formation of the Three Layers in Sea-Urchins

The simplest kind of gastrulation looks just as though
one side of the blastula was being pushed and folded
inwards by an invisible finger, in the same way in
which one can push in one side of a rubber ball till
it touches the other side. This happens, for example,
in the embryos of sea-urchins and starfish. The first
sign of gastrulation is a flattening of the bottom of
the blastula, where the cells are usually slightly
bigger than at the top, although this difference is
not very striking, since there is not much yolk in
the egg. Soon the flattened part sinks deeper in
towards the centre of the blastula and makes a
groove or small hole. This hole is a very important
structural feature and turns up under all sorts of
peculiar guises in other groups; it is called the
blastopore, and is the entrance to the cavity lined by
the endoderm, or the primitive gut. It grows deeper

42 HOW ANIMALS DEVELOP

and deeper as gastrulation goes on. The third layer
or mesoderm consists of a loose mass of cells, which
separate off from the endoderm (Fig. 8).

In Frogs and Newts

A rather more complicated gastrulation process
occurs in newts and frogs, which belong to the group

fries

Fig. 8. — The blastula {A) and gastrula {B) of a sea-urchin. The
mesoderm is being, formed from the endoderm in {B). (From

MacBride, after Field.)

of Amphibians. All amphibian eggs contain a fair
amount of yolk, which, as has been described, makes
the blastula asymmetrical and gastrulation rather
more difficult ; moreover, being more highly evolved
creatures than sea-urchins, their gastrulation has
diverged more from the simple ideal type. In fact,
it is only by the application of modern methods of
investigation that we have found out what actually
happens. All the old methods involve killing the
embryos at different stages in their development and
comparing them. The embryos are usually killed in
such a way as to make them very hard, and then,

e

Fig. 9 a— Development of the newt's egg. {a) The blastula in its membranes, (b) View

from underneath of the early gastrula showing the beginning of the blastopore.

(c) Later view of the round blastopore, {d) View from aljove of the slit-like blastopore

at the end of gastrulation. (e) Later view showing the open neural plate

Fig. gb - Operating on a newt's embryo. The embryo lies in a glass dish lined
with wax. 1 he operator has a glass needle in the left hand and in the right
hand a hair-loop on a glass-holder ; the loop can just be seen crossing the embryo

MOVEMENTS AND FOLDINGS 43

after embedding them in wax, they can be cut into
thin slices or sections. These sections are then stained
to bring out the different structures, and one can
thus find out what the internal anatomy of the
embryo is like. But for investigating the changes
going on in gastrulation a very much improved
method has been recently worked out, chiefly by
Professor Vogt of Zurich. When gastrulation is
beginning, the embryo is placed for a few minutes
against little blobs of jelly which have been soaked
in dyes. The cells of the embryo which are in contact
with the jelly absorb the dye and become stained
themselves, showing up as coloured patches on the
surface of the blastula. If the dye is chosen rightly
it is not poisonous, and the cells remain quite
healthy and the embryo proceeds with its gastrula-
tion. All one has to do in order to follow the
gastrulation is to watch the dyed patches and see
how they move. The whole process can be followed
in one and the same embryo, and there is no need
to rely on the comparative study of a whole set of
specimens of different ages.

Figure 9 a shows photos of a newt embryo during
gastrulation. In the first photo gastrulation is just
beginning, and a slight crescent-shaped groove has
appeared on the surface of the blastula. This is the
beginning of the blastopore. In the newt it does not
lie right at the bottom, as it did in the sea-urchin,
but rather to one side (see Fig. 10, a). From the
outside, without the aid of coloured marks, all we
can see is that the blastopore first becomes bigger,

44 HOW ANIMALS DEVELOP

and the horns of the crescent spread round till they
join up to form a circle, which encloses the whole
yolky bottom part of the egg; it then becomes
smaller again, pushing the yolky cells inside, and
closes up to a tiny slit, and eventually disappears.
Just about at the slit stage a sinuous ridge appears
on the surface of the embryo, marking off a horseshoe-
shaped area, which is darker in colour than the rest.
The sides rapidly get nearer together, and the
horseshoe-shaped area becomes squeezed up to a
dumb-bell shape, and finally to a deep groove. The
dark area is known as the neural plate, or groove,
according to the stage at which it has arrived. It is
the first rudiment of the brain and central nervous
system, and, as we shall find, gastrulation is com-
pleted before it appears; an embryo in which the
neural plate can be seen is no longer called a gastrula
but a neurula.

Fig. 10 shows a stain experiment from which one
can discover what is really going on all this time.
The first figure shows a series of patches made at
the beginning of gastrulation, arranged in a ring
round the blastopore. In the stages illustrated in the
next two figures the blastopore becomes round and
then closes up to a slit, and as it does so the patches
move in towards it and disappear inside, so that
when the neural plate has developed, in Fig. lo, ^,
nearly all the coloured patches have been swallowed
up. A section through the embryo at this stage shows
that all three layers have been formed and that the
coloured patches lie in the middle layer or mesoderm.

MOVEMENTS AND FOLDINGS

45

2 1

^ 5

Fig. io. — One of Vogt's dye experi-
ments, showing the disappearance of
the mesoderm through the blastopore.
(e) Is a section showing the marks in
the mesoderm under the neural plate.
(From Diirken, after Vogt.)

46

HOW ANIMALS DEVELOP

They have moved nearer together and lie underneath
the thick neural plate. The primitive gut is repre-
sented by a narrow hole, and a thick mass of
endoderm, which was made from the yolky cells
lying at the bottom of the blastula, inside the ring
of coloured patches.

a b

Fig. 1 1. — Vogt's map of the presumptive areas of the newt's gastrula
{a), and Weissenberg's map for the lamprey [b). Side view; the large
arrows ma^k the position of the blastopore. Widely spaced oblique
lines, skin; close oblique lines, neural plate; dotted, mesoderm;
white, endoderm. The directions of cell movements are also shown

on Vogt's map.

A large number of such experiments have been
made, and we know exactly where each part of the
blastula goes to during gastrulation. The easiest way
to summarize this information is to make a map,
showing for each region the organ into which it will
develop. It is usual to speak of mesoderm before it
has arrived at its final position as "presumptive
mesoderm" and of the material which will turn into
the neural plate as the "presumptive neural plate,"
and so on. We can therefore call this map a map of
the presumptive areas. Vogt's map for the early newt
gastrula is given in a rather simplified form in Fig. 1 1 , a,

MOVEMENTS AND FOLDINGS 47

which also shows the directions in which the various
regions have got to move to get to their final
positions. The whole top of the blastula turns into
ectoderm, the part nearest the blastopore into neural
plate, the rest into skin. The presumptive endoderm
lies at the bottom, and the presumptive mesoderm
is an irregular ring between them, widest just in
front of the blastopore. It is surprising to see the
enormous movements which the tissues carry out.
The presumptive skin has to expand so as to cover
the whole surface ; the presumptive neural plate has
to swing in towards the middle line, while the
presumptive mesoderm gets out of its way by diving
into the blastopore and growing forwards along the
inside. The endoderm is more passive, and is carried
along by the other parts of the embryo. Nobody
knows quite what makes these movements happen,
or where the force comes from to push the tissues
along. But already at the beginning of gastrulation
the various regions have tendencies to behave in the
appropriate way. If different bits of tissue are cut
out and grafted back into other parts of the blastula
(by a method which will be described more fully
later), they go on behaving in their own typical
fashion even in the wrong situation ; the presumptive
skin stretches in area, the presumptive mesoderm
sinks in and disappears, and so on.

If we leave the coloured patches a bit longer, we
can soon find out what the three layers develop into.
We find that, as was said above, the ectoderm forms
the neural plate, which turns into the brain and

48 HOW ANIMALS DEVELOP

central nervous system, and also the skin. The
mesoderm develops into the main muscles and
skeleton of the body, and the endoderm forms
the gut and all the organs which are derived
from it later in development, such as the liver and
lungs, etc.

Although gastrulation in the amphibian embryo is
more complicated than in the sea-urchin, it is obvious
that the two processes are similar in many ways. In
both the net result is to finish up with three layers,
and in both we find a blastopore and a primitive
gut. But in the amphibia the mesoderm is formed
directly from the skin of the blastula, and is not
given off secondarily by the endoderm. Moreover,
in the amphibian egg the process involves an active
movement down to the edge of the blastopore, then
a dive inside and movement again away from the
blastopore along the inner surface, while in the
sea-urchin the material simply folds in as a whole
and there is not so much movement over the edge
of the blastopore.

Lampreys

The '* stain experiment" has not yet been performed
on many groups of animals. Besides the amphibia
worked out by Vogt, Weissenberg has done experi-
ments with the lamprey, and Wetzel has given a full
account of the gastrulation of the chicken. We need
not give much description of the development of the
lamprey, since it is extremely like the process we
have just described in the newt. Fig. 11,^, shows

MOVEMENTS AND FOLDINGS 49

Weissenberg's map of the presumptive areas, and
the similarity with Vogt's map is immediately
obvious. It is an impressive example of the way in
which different groups, here the fish and the am-
phibia, resemble one another in their early develop-
ment. It should be mentioned, however, that the
lampreys are a very primitive type of fish ; the more
highly evolved types have very yolky eggs and a
different sort of gastrulation.

Birds

The chick embryo is a classical object for embryo-
logical investigations. The first studies we know of
were made by Aristotle, and for a very long time
no one looked more deeply into the matter than he
had. The first sign of development which he could
see was the appearance of a pulsating heart which
is full of red blood and very large and obvious in
the early stages. But gastrulation takes place still
earlier, when the embryo is so small that the details
can hardly be made out without a lens or a micro-
scope. The process is, however, particularly in-
teresting, because it is in some ways transitional to
the conditions found in mammalian and human
embryos. Both birds and mammals are evolved from
extinct reptiles, and are therefore related to one
another, though rather distantly.

The bird's tgg^ like the reptile's tg'g, contains a
very large amount of yolk and undergoes the dis-
ooidal type of cleavage described in the last chapter,
ibrming a blastula which consists of a little disc or

50 HOW ANIMALS DEVELOP

cap of cells lying on top of the yolk but separated
from it by a small cleft representing the blastula-
cavity.

As in the sea-urchins, the gastrulation takes place
in two stages, first the separation into ectoderm and
endoderm and then the formation of the mesoderm.
In birds the mesoderm is developed from the ecto-
derm, not from the endoderm. The endoderm for-
mation takes place very early, usually before the egg
is laid. In the posterior part of the little disc, which
is called the blastoderm, cells sink down and then
turn underneath and grow forward along the under
surface until the whole area is provided with a
second layer, with ectoderm above and endoderm
below. When the egg of a chicken is laid, the blasto-
derm is already in this two-layered condition, and
it is also divided into a central transparent area,
where the embryo will develop, and an outer ring
which is opaque because the endoderm cells there
contain a great deal of yolk. The outer opaque area
develops into various specialized organs for absorbing
the yolk, and will not concern us any more in this
chapter.

The changes which go on in the transparent area
have been investigated by two new methods, and
although their results are in almost complete
agreement with one another, it is difficult to recon-
cile some of their details with observations based
on the old methods. One of the new methods is
similar to Vogt's, and depends on watching what
happens to coloured patches made with non-poison-

MOVEMENTS AND FOLDINGS

51

ous dyes ; the other is to take cinematograph photos
of the development. The cinema photography can be
done in two ways : Graper removed part of the
shell over the embryo, stained the whole embryo
with a non-poisonous dye so as to make it easier to
see, and photographed it by reflected light: while
Waddington and Canti took the whole embryo out

EMBRYO

WATCH GLASS

PETRI DISH

COTTON
WOOL

WATER

NUTRITIVE
MEDIUM

Fig. 12. — Glass culture vessel for growing embryos.

of the shell, cleaned the yolk off it, and put it on
the surface of a nutritive jelly in a culture-vessel
(Fig. 12), where it went on growing and developing
and could be photographed as a transparent object.

When the egg is laid, then, the blastoderm has
already developed for several hours after being
fertilized in the body of the mother, and consists of
a circle of transparent tissue surrounded by a ring
of opaque tissue, both these areas being two-layered.
The first thing that happens is that some of the
ectoderm-cells collect together into a thickening
which appears in the posterior part of the trans-
parent area, and grows forward till it stretches as a

52 HOW ANIMALS DEVELOP

narrow ridge across about three-quarters of the area.
It takes about eighteen hours to grow to its full
length, which is about 3 mm., so the rate of elonga-
tion is not excessively fast, only about a yard a month.
The mesoderm is produced from this ectodermal
thickening or primitive streak, first in its front end
and gradually further and further back. When
mesoderm production begins the tissue at the sides

ECTODERM

MESODERM

ENDODERM

Fig. 13. — Section across the primitive streak of the chick
showing the origin of the mesoderm

moves straight across the transparent area towards
the primitive streak, dives down into it from each
side, turns round, and grows out towards the sides
again between the ectoderm and the endoderm
(Fig. 13). If a little finely ground Indian ink is put
on to the surface of the primitive streak and the
embryo grown for a few hours in a culture vessel,
sections will show how the Indian ink has been
picked up by cells which originally lay on the surface
and has been carried down into the mesoderm.

Finally, one more movement happens. The
streaming in towards the primitive streak ceases,
first in the front end, and instead a strong backward

MOVEMENTS AND FOLDINGS 53

movement begins within the streak. The streak, in
fact, gets shorter again, telescoping up along its
length. The movement causes the front part to be
drawn out, like glass in a flame, and as it becomes
thinner and longer this part separates off from the
rest of the streak and becomes the neural plate and
the mesodermal rudiment of the backbone. This
mesoderm does not remain as a flat plate, but soon
breaks up on each side of the neural plate into a
series of little lumps, the body-segments, which are
found in all embryos at this stage, but are more
obvious in the chick than in the other embryos
which have been described. Between the two rows
of segments, immediately beneath the neural plate,
is a continuous strand of mesoderm, which is the
first part of the backbone to be developed.

In a map of the presumptive areas at the stage
w^hen the primitive streak is fully grown but before
the backward movement has begun, the presumptive
neural plate and presumptive body segments and
backbone are concentrated at the front end. The
map in Fig. 14 shows this clearly for the neural
plate. It is not very easy to compare this with the
map for the newt, because in the newt the endoderm
and mesoderm are formed together and in the chick
are formed separately. The chicken has what may
be called an "endoderm-blastopore" in the posterior
of the blastoderm before the primitive streak appears,
and Graper thinks this should be compared with
the newt blastopore; but Wetzel thinks the com-
parable structure is the later "mesoderm-blastopore"

54 HOW ANIMALS DEVELOP

in the front end of the primitive streak. The difference
of opinion shows how doubtful the question is : in
some ways one comparison is more informative, in
some ways the other. In both cases in front of the

Fig. 14. — Map of the presumptive areas in the chick,
in the late primitive-streak stage, aged 18 hours. Only
the transparent area is shown. The arrows show the
directions of movement and the primitive streak is
drawn black. Widely spaced vertical lines, skin; close
horizontal lines, neural plate; dotted, mesoderm. The
endoderm lies underneath the whole surface

blastopore there is a zone of presumptive mesoderm
and outside that a zone of presumptive neural plate,
just as there is in the newt or lamprey. In the map of
the later stage (Fig. 14) part of the mesoderm has
already disappeared inside.

Mammals

We must now go on to consider the development of
mammals, but it will only be possible to give a very

MOVEMENTS AND FOLDINGS 55

rough sketch of their gastrulation in the space
available, because different members of the group
have evolved quite different ways of developing.
Probably the extreme diversity of the processes of
gastrulation in mammals is due to the difficulties
raised by the fact, so advantageous in many ways,
that the embryo remains in the maternal womb.
There are actually two main problems which arise.
In the first place, although the mammals are derived
from reptiles whose eggs contain a large quantity of
yolk, they themselves produce eggs which are
extremely poorly provided with yolk, all the necessary
nutriment being derived from the mother. Secondly,
a whole set of organs have to be developed to make
an adequate connection with the wall of the womb.
The mammal, having evolved through a stage with
yolky eggs, recapitulates this stage in its develop-
ment, in accordance with Haeckel's recapitulation
hypothesis, but it converts the organs which in its
ancestors were used to absorb the yolk into the
placenta and other organs by which it is attached
to the mother. The placenta is porous, and allows
oxygen and food substances to diffuse from the
maternal blood into the embryonic blood, which is
carried along the blood-vessels in the umbilical cord
into the foetus, which is thereby nourished and
sustained.

The mammalian embryo, again like its ancestors
the reptiles, goes through a primitive streak stage,
but as the tgg contains very little yolk it arrives at
this stage in rather a different way. The cleavages

56 HOW ANIMALS DEVELOP

are quite normal: they are total and nearly equal
A blastula cavity appears in the usual way, and
the cavity grows to an enormous size (Fig. 15). The
walls are very thin, only one cell thick, except at
one place where there is a little lump of cells hanging
down inside like a drop or a swarm of bees. This
lump is the inner cell mass and eventually develops
into the embryo, while all the rest of the thin- walled
blastula develops into placenta, etc., and corresponds
to the opaque area in the chicken's tgg.

The endoderm forms by a process which is so
simple that it can hardly be called a gastrulation ;
the lowest layer of the inner cell mass simply grows
out in all directions till it covers the inner surface
of the blastula. Sometimes the mesoderm, or at least
part of it, forms in a similar way by differentiating
in situ from the cells of the middle part of the inner
cell mass. But some mesoderm is also formed as it is
in chicken. That is to say, it comes from the primitive
streak, which appears on the top of the inner cell
mass, in the upper layer of cells, which is the
ectoderm. Part of the inner cell mass may also split
off to form more of the non-embryonic apparatus,
but the embryo always passes through a stage when
there is a thickened area, the upper layer of which is
the ectoderm with the primitive streak, the lowest
layer the endoderm, with probably some mesoderm
between. It is not known exactly how much meso-
derm is formed by the primitive streak, and no
staining experiments have been done, so it is im-
possible to give anything like an accurate map of

MOVEMENTS AND FOLDINGS

INNER CELL
MASS

57

ENDODERM

TROPHOBLAST
ECTODERM

Fig. 15. — The development of the rabbit, {a) and {b) are sections through
the whole egg showing the formation of the endoderm, {c) is a surface
view of the primitive streak which develops on the inner cell mass, and
(d) (from Quain's Anatorny) is a much later stage showing the gill slits

58 HOW ANIMALS DEVELOP

the presumptive areas. It may be possible to work
out such a map in the near future by growing the
embryos in cultures like the chicken embryos. It is
already quite possible to keep rabbit embryos alive
for a few days, so that they develop fairly normally,
and it should not be very difficult to improve this
technique slightly. But the suggestion that man will
soon be born out of bottles is very optimistic (or
pessimistic, according to the point of view). The
technique of cultivating embryos will probably
remain a useful scientific method for a long time,
but it is difficult to imagine it being used practically.
The mammalian embryo, including the human
embryo, therefore goes through a primitive streak
stage very like a chicken. Although we do not yet
know much about the details of what is happening,
there are various reasons for believing that the
movements which take place are similar in both
sorts of animals. We can draw this conclusion from
some of the kinds of abnormal embryos which are
found. Gastrulation is a process involving such
complicated movements that it is quite easily upset.
For instance, the material which moves forward to
build up the primitive streak may for some reason
go awry and split into two separate streams, so that
it makes two front ends of the streak, and the
embryo develops with two heads. Or a similar
splitting may happen later, when the presumptive
neural plate and body-segments are being pulled
backwards into their final positions, and we then
get two posterior ends in the embryo, which is split

MOVEMENTS AND FOLDINGS 59

part way up the back. Both these sorts of monstrosi-
ties sometimes occur in man, if anything happens
to disturb development, but the embryo is so well
guarded from casual disturbances, well hidden as it
is in the womb, that they are fortunately rare.

It is interesting to notice that mammalian embryos
are relatively very slow in arriving at the primitive
streak stage of development, but then run ahead
quickly till the main parts of the body are present,
slowing down again, in the case of man at least, for
the final elaboration of the parts before birth. Exact
comparisons of the number of days taken by different
embryos to arrive at comparable stages are not very
informative; what is important is not the absolute
times but the relative times for various amounts of
development within the same life-history. Thus a
newt takes about one day to get to the beginning of
gastrulation, about one day to gastrulate, and about
two days to develop from the end of gastrulation to
an embryo with fifteen body-segments (the times
actually depend on the temperature, since the
warmer the egg is kept the faster it develops; but
the temperature does not seriously affect the relation
between these lengths of time). A rabbit embryo
takes nearly eight days to get to the beginning of
gastrulation, and then like the newt about one day
to gastrulate and two to develop into an embryo
with fifteen body-segments. A human embryo takes
about a fortnight before arriving at the primitive
streak stage. This slowness in early stages, and speed
in later stages, is probably due to the fact that

6o HOW ANIMALS DEVELOP

development within a womb is a fairly new idea in
evolution ; mammalian embryos are not yet perfectly
adjusted so as to take advantage immediately of the
favourable condition which a womb provides.

The length of time between conception and birth
is different in different mammals. On the whole, the
bigger the animal the longer the time, but there is
not a strict proportionality; the smaller ones take
longer than would be expected, and so does man.
In elephants the time is about 620 days, during
which time new elephant tissue is formed at an
average rate of 14 lbs, per day, while the mouse,
which is only one-quarter-millionth as big, takes
21 days to produce an infant, making new "mouse'*
at the rate of only a fiftieth of an ounce per day.
Bigger animals also live longer than smaller ones,
and the whole tempo of their lives is slacker. Perhaps
each animal has its own apprehension of time, so
that for instance a mouse feels a minute of man-time
as a whole quarter-of-an-hour of mouse-time, while
to the elephant it is only a few seconds of elephant-
time.

CHAPTER IV
THE "ORGANIZATION CENTRE"

If we observe the development of an egg, it is fairly
easy, as we have shown in the previous chapters, to
find out what each part develops into, but much
more difficult to discover why it develops as it does.
But the solution of this problem is fundamental for
an understanding of living organisms. It was pointed
out in the first chapter that the functioning of living
animals depends on their structure and, since they
are not man-made machines, but are such that
the ability tp develop is an essential part of their
nature, we have to be able to give an account of
how this structure arises before we can understand
them.

One cannot expect to answer at once the question
of why an egg develops at all. It must be unstable
in some way which we do not understand, and bound
to begin changing and developing as soon as it is
fertilized. But it is better to begin investigating
something simpler; let us ask, why does one part of
an egg develop into one organ and another part into
another? The factor which determines what a given
part of the egg will become, or determines its
developmental fate, as it is called, might be either inside
or outside the piece of material in question. That is
to say, it may be that a given piece of the egg will
develop in accordance with a pre-determined

62 HOW ANIMALS DEVELOP

developmental fate under any conditions in which it
can develop at all, or, on the other hand, the
development of the piece might be directed by some-
thing outside it. Both possibilities are actually
realized. In the first case the piece is said to be
determined and to be capable of self- differentiation. In
the second case the tissue is undetermined, and the
external factor which determines it may be either
in the other parts of the tgg or else outside the tgg
altogether. It is unlikely that all the determiners will
be outside the tgg^ since it is difficult to suppose that,
if an Ggg is floating in the sea, for instance, the sea
water surrounding its different parts would be
sufficiently dissimilar to cause the development of a
whole set of organs. Actually the external determiners
are mainly important in very early development
though they are active again to cause minor modifi-
cations towards the end of embryonic life. The first
difference between the various parts of an tgg must
in any case be externally determined, either during
the process by which the egg is formed in the body
of the mother or soon afterwards; if the o^gg is
originally made with all its parts exactly alike it
cannot on its own develop special characteristics in
its different parts because there is no reason why a
special character should arise in one part rather than
another. Actually it is found that all eggs are made
with certain differences between the parts ; there is,
for instance, an animal pole at the top and a vege-
tative pole where the yolk is collected at the bottom.
Often the entry of the sperm at a definite point is a

THE *'ORGANIZATION CENTRE*' 63

further important external determining factor. But
the number of these early external determiners is
comparatively small, and the most striking steps in
development are caused by internal determiners.

The Technique of Micro-Surgery

The first experiments which were successful in
locating these determiners inside the embryo were
carried out by Spemann. He used two species of
newts, one of which, Triton cristatus, lays a white egg,
while the other, Triton taeniatus, lays a rather dark-
coloured egg. Spemann first had to work out a
technique for making operations on these eggs. The
eggs themselves are embedded in two layers of jelly,
but these can be removed fairly easily. However,
when the eggs have been made free in this way,
there are further difficulties because the eggs are so
small, only about 2 mm., or a tenth of an inch,
across. Spemann invented two special instruments
for cutting such small masses of tissue ; one is made
of very fine glass drawn out to a sharp point, much
finer than any point which can be made on a pin, and
the other is a little loop of baby's hair, mounted on a
holder, which can be used as a knife. All the opera-
tions have, of course, to be performed under a
microscope.

The advance of experimental embryology is always
waiting on two things, the invention of new instru-
ments and methods, and the training of people with
sufficient manipulative skill to use them. Spemann's
instruments were the first which were invented for

64 HOW ANIMALS DEVELOP

the purpose of making very minute operations on
embryos. They are not difficult to use moderately
well, but it requires years of practice to become
really skilful with them. For working on chick
embryos, which will be discussed on page 70 f, Spe-
mann's instruments are useless because the tissue is
too tough to be cut with the fine glass points; one
has to use coarser steel knives, which are rather more
difficult to handle. No one has yet invented instru-
ments really suitable for working on mammalian
embryos, and that is partly why we know so little
about them. The tissue is so sticky that it clings to
the end of a knife, and if one tries to scrape it off, it
usually gets torn to bits and spoilt; this small tech-
nical difficulty makes the most important experiments
impossible to perform.

The Focus around which the Embryo is Integrated

Speman's first experiment was to make an exchange
between a piece of white presumptive skin of
cristatus and a piece of brown presumptive neural
plate of taeniatus. He did the same operation at
various stages of development, and found that if the
exchange was made between two early gastrulae
the result was quite unlike what happened if it was
made between late gastrulae. When the experiment
was done in the early stage, the piece of white
cristatus presumptive skin which had been grafted
into the neural plate region of the taeniatus cgg^
developed into neural plate like its surroundings;
and the brown taeniatus presumptive neural plate,

THE "organization CENTRe" 65

having been grafted into the cristalus skin region,
developed into skin (Fig. i6). Both the pieces of tissue,

Fig. 16. — Spqmann's exchange experiment (from Diirken, after
Spemann). {a) A gastrula of Triton alpestris with a small dark
implant of the presumptive neural tissue from Triton taeniatus.
{b) The alpestris embryo at a later stage with the taeniatus tissue
forming part of its skin

in fact, developed in accordance with the region
into which they were grafted, and not in accordance
with the region from which they originally came.

66 HOW ANIMALS DEVELOP

They did not self-differentiate and therefore cannot
have been determined when the experiment was
made: their fates must have been determined by
something in their new situations. When the experi-
ment was made in the late gastrula stage, the result
was the exact opposite. The white piece of pre-
sumptive skin developed as skin although it was lying
in the middle of the taeniatus brain, and the trans-
planted piece o^ taeniatus presumptive brain developed
into a little patch of brain lying in the middle of the
cristatus skin. The determiner, then, must have
finished its action by the late gastrula stage, so that
the parts of the egg are by that time determined and
must self-differentiate. This fixed the period during
which the determiner works.

Spemann then began to examine the various parts
of the gastrula, trying to locate the determiner. He
got his first hint of where to look from the following
experiment. He took a young taeniatus gastrula, cut
it in half with a horizontal cut, and then turned
round the top half through half a turn and replaced
it in its new position. A glance at Vogt's map of the
newt gastrula (Fig. 1 1 ) will show what he had done ;
he had exchanged the presumptive skin and neural
plate areas. However, the gastrula healed up again
and went on developing. The neural plate appeared
in front of the blastopore as usual ; in fact, in its
normal position as regards the bottom half of the
egg. But it was in an abnormal position as regards the
top half and must have been made out of presumptive
skin. This shows that the determiner must be in the

THE "organization CENTRE*' 67

bottom half; Spemann suggested that it is actually
located near the blastopore.

A few years later Spemann and his pupil, Hilde
Mangold, tested this suggestion. They removed the
blastopore region from a young cristatus gastrula and
grafted it into the belly region of a taeniatus gastrula.
The taeniatus gastrula, which thus had two blasto-
pores, developed two neural plates, and two
complete sets of embryonic organs (Fig. 17). This
might have been due simply to a self-differentiation
of the grafted blastopore, but Spemann and Mangold
showed that this was not a complete explanation.
Owing to the differences in colour between the cells
of the taeniatus host and the cristatus graft, they could
tell how the secondary embryo was built up.
Examination showed that the grafted blastopore had
developed chiefly into mesoderm, which was its
presumptive fate, while the neural part of the
secondary embryo had been formed from the tissues
of the host. The mesodermal part therefore had
arisen by self-differentiation of the grafted blastopore,
but the neural part had not. It had been induced out
of host tissue which would ordinarily have formed
skin. The implanted blastopore had therefore
determined the fate of this presumptive skin, causing
it to become actual neural plate. This experiment
definitely locates the determiner at the blastopore.
It was later showTi that the whole ring of mesoderm
which lies in front of the blastopore in Vogt's map
is capable of determining, though this capabiHty is
strongest just near the blastopore and becomes

Pr. med.

Sec. med.

sec. and.

\l^' ^7-— An organizer graft in the newt (from Durken, after Spemann and
Mangold), (a) Shows the neural groove of the host embryo with the induced
neural groove on the left, (b) Shows the induced neural groove more clearly.
(c) Is a later stage, the host's neural tube is on the right and the induced neural
tube runs straight up the middle, (d) Is section with the host's neural tube on
the left {pr. med.) and the induced neural tube {sec. med.) on the right, with an
induced ear (/. sec. aud.) beside it

THE "organization CENTRE*' 69

weaker further away from it. Spemann gave the
name of organizer to pieces of tissue which can
determine in this way, and of organization centre to
the part of the embryo where they occur, but these
two names are often used more or less interchange-
ably in a rather loose way. The organization centre
is the whole presumptive mesoderm, which, as we
know, sinks in through the blastopore and grows
forward along the inside. Finally the mesoderm
spreads over the entire embryo between the ectoderm
and the endoderm, but at first it forms a narrow
tongue which is the roof of the primitive gut, and it
is in this stage that it determines the ectoderm lying
immediately above it to become neural plate, while
all the rest becomes skin.

The importance of the organization centre can
be exhibited in two ways. One way is to point out
that it causes part of the gastrula-ectoderm to
develop into neural plate. This property is important
enough, but other similar development-provoking
agents, or determiners, had previously been dis-
covered. The special importance of the organization
centre is better conveyed by the name Spemann
actually chose ; it is that part of the embryo with
respect to which all the rest is organized. In order
to describe the behaviour of any part of a newt
gastrula, it is necessary and sufficient to specify
its relation to the organization centre. Spemann' s
name for his discovery may at first sight seem
rather grandiloquent, but is really quite reasonable
and accurate.

70 HOW ANIMALS DEVELOP

Birds

This discovery is so fundamental that we must go
on to see if it applies to other animals and try to
find out if they also have organization centres. Work
which has been carried out since Spemann's original
experiments has shown that in fact organization
centres are not merely a speciality of the newt's tg^,
of no general importance, but, on the other hand,
can be found in nearly all groups of vertebrates and
in some invertebrates. The one which is perhaps
most similar to the amphibian organization centre
has been found in the birds, but, as we might expect,
there are differences correlated with the differences
in gastrulation in the two groups.

As was described in the last chapter, the endoderm
and mesoderm are formed separately in the bird,
while in the newt they are both formed at the same
time as the blastopore. We find that not only are
the formative functions of the newt's blastopore
shared between two structures in the bird but so are
its organizing functions. There are, in fact, two bird
organizers instead of one ; the first is concerned with
the formation of the endoderm, the second with that
of the mesoderm.

All the experiments with birds were done on
chicken or duck embryos which were kept in culture
after they had been operated on. The first experi-
ment was concerned with the endoderm. This is
already formed when the tgg is laid, so there is
no possibility of transplanting the ''endoderm-

■§

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4)

■5
•5

i-

o "-^

.-3 QJ

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V o

f^ Si

bfJ5

CO

:y^m

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(K4

<«^^« A ^..'» . r^,^^^ ^^^, ^^»»

THE ORGANIZATION CENTRE 7 1

blastopore." Instead, young embryos were taken at a
stage when the primitive streak or thickening had
just appeared ; the endoderm was removed, and
then replaced after being turned round through
1 80 degrees, so that the part which originally lay
under the primitive streak in the posterior region
near the endoderm-blastopore now lay under the
other, anterior end. In some of these operated
embryos an extra primitive streak appeared in the
anterior end, where it had been induced by the
endoderm coming from the endoderm-blastopore
region, which is therefore an organization centre.
Meanwhile the original primitive streak, which had
been induced by the endoderm before the operation
was made, continued to develop, so that finally two
embryos appeared on the one blastoderm.

The next experiment dealt with the formation of
the mesoderm from the primitive streak at a rather
later stage. It is easy to take a piece of primitive
streak from one embryo and place it between the
ectoderm and endoderm of another; it develops
by self-differentiation in its new situation into its
presumptive fate, which is mesoderm and a little
neural plate tissue. But the important thing is that
the host ectoderm lying above it, which ought to turn
into skin or part of a yolk-absorbing structure, now is
induced to form a secondary embryo with a neural
plate and other organs. This proves that at least some
of the presumptive mesoderm, that part which lies at
the front end of the primitive streak, is also an organ-
ization centre (Fig. i8), as it is in the newt embryo.

72 HOW ANIMALS DEVELOP

Mammals

Organizers have been found in other groups still
more widely removed from newts. We know rather
little about the organizers in mammals : in man we
have no certain knowledge at all of them. But it has
been proved that the rabbit embryo can react to a
chick primitive streak organizer and can be induced
by it to develop an extra neural plate. This suggests
that the mechanism is essentially the same in
mammals as in the other groups and that they also
have organizers, but it has not yet been possible to
make organizer grafts because of the technical
difficulties mentioned before (p. 64). This experi-
ment also shows how extremely unspecific organizers
are. It seems that an organizer from any group
of animals will work on the embryos of any other
group. Probably, as is discussed later (p. 94), the
activity of the organizer is due to a chemical sub-
stance, and this may very likely be the same substance
in all the different groups of vertebrates.

Sea-urchins

Among the invertebrates, Horstadius has discovered
an organization centre in the sea-urchin embryo
which is very like, though slightly different from,
that of the higher animals. The sea-urchin's tgg^ as
was described earlier, has a very simple gastrulation ;
the blastula is spherical, with all the cells more or
less equal in size, and in gastrulation the bottom of
it just draws back into the inside. Gastrulation

<t^-^^ A «,.^ » r^-^^r ^-^..T,^^,^"

THE ORGANIZATION CENTRE 73

occurs quite soon after fertilization, when the
cleavage cells are still rather large; and if one
attempts to make grafts such a large proportion of
cells get injured in the operation that the experiment
is not a success. So Horstadius did his operations still
earlier, during the cleavage, when he could cut in
between the cells without injuring them. Most of the
experiments were made when the egg had divided
into sixteen cells. The cleavages are not quite equal,
and the sixteen cells are arranged in three circles, one
at the top consisting of eight moderate-sized cells,
then a circle of four large cells, and at the bottom a
circle of four small cells (Fig. 19). Horstadius cut the
embryo in half in various ways and then joined the
halves together again. He found that several, but not
all, combinations of halves could regulate themselves
so as to produce a normal larva. He also found that
wherever the small vegetative cells were grafted, they
started sinking in and turning into endoderm, and
moreover they carried the surrounding cells in with
them and induced them to become endoderm. They
therefore acted to some extent like an organizer. We
shall discuss in Chapter vi the way in which this
organization centre seems to differ from that of the
newt.

Insects

In the insects another sort of organization centre has
been found which is still more different from that
of the newt. It was discovered by Seidel, who worked
on dragon-flies' eggs. We have not said anything

^ ECTODERM

ENDODERM

Fio. 19. — Grafting experiment in sea-urchins, {a) Shows the normal

i6-cell stage; in {b) a top half of one egg (dotted) is combined with a

side half of another, (c) Is a section of the resulting blastula showing

some of the dotted material turned into endoderm

THE "organization GENTRE" 75

about the development of insects yet, and it is rather
unUke the development of most other animals. The
egg is a banana-shaped object, containing a large
amount of yolk. The nucleus, after it is fertilized,
lies nearly in the middle. The ^'cleavages" consist of
divisions of the nucleus without any accompanying
divisions of the whole mass of yolk, so we find
gradually more and more nuclei scattered about
throughout the egg, till the whole yolk is full of them.
After a time the nuclei collect on the surface and
cell boundaries form round them, so that eventually
a stage is reached with the yolk nearly empty of
nuclei and covered with a cellular skin. This is called
the blastoderm stage and corresponds to the blastula,
only here the blastula cavity is filled up with yolk.
Then gastrulation takes place, starting with a sinking
in of the blastoderm-skin at one side of the embryo
(Fig. 20).

Seidel tied thin hairs round the egg in the early
"cleavage" stages, and thus constricted the egg into
two parts. He then watched how each part developed
and in this way could discover the influences each
part had on the formation of the embryo. He found
that there is an essential region in the bottom end
of the egg. He called this an activation centre, and it
is not quite the same as an organization centre,
because it does not determine the way in which the
various parts of the egg will develop. What it does
do is to activate another centre which lies further
towards the front of the egg. This other centre, which
is called the differentiation centre, lies, in fact, just

76 HOW ANIMALS DEVELOP

where the embryo begins to be formed by the thick-
ening and sinking-in of the blastoderm. One might
almost say that it lies at the blastopore, like the other
organization centres, but the gastrulation of the
insects is so a-typical that such a comparison is
doubtful. In any case, the differentiation centre is

DIFFERENTIATION
CENTRE

ACTIVATION
CENTRE

b c

Fig. 20. — Diagram of the development of the dragon-fly. {a) Shows
the egg- and sperm-nuclei just about to unite, (b) Is an early cleavage
stage with the activation centre, (c) Is the "blastula" stage, with many
nuclei lying on the surface, when the differentiation centre is active

much more like an organization centre in its activity
than is the activation centre. As soon as it has been
activated it starts to form a complete embryo round
itself. If part of the tgg is tied off with a hair, so
that only a small region remains connected with the
differentiation centre, nevertheless a complete em-
bryo may be developed in the part. This means that
the centre alters the fate of the tissues around it and
determines how they shall develop so as to give a
complete embryo. Seidel discovered how at least
the first step of this determination is done. The dif-

THE "organization centre" 77

ferentiation centre starts a wave of contraction pass-
ing through the yolky core of the egg, and as the
yolk contracts away from the outer skin of the egg,
a hollow is left in which the blastoderm cells rapidly
collect and begin to develop into the embryo. If part
of the egg is tied off with a hair, this hinders the
progress of the wave of contraction, which adjusts
itself to the amount of space which is available to it.

Seidel also found out something more about the
activation centre. He showed that it could only be
formed if the early cleavage nuclei are allowed to
wander down to the bottom end of the egg, where
they react in some way with the cytoplasm there
and set free a substance which diffuses forward again
through the yolk to the differentiation centre.
Neither the nuclei alone, nor the particular region of
cytoplasm, can act effectively.

There is one very important respect in which all
the organization centres we have described are alike,
except the Activation Centre, which is rather in a
class apart. Not only do they all become active when
gastrulation starts, but they are all located at the
centre of the gastrulation movements, that is to say,
at the region of the blastopore. This is true both
when it is endoderm which is being formed, as in
the sea-urchin or the first chick organizer, and when
the important process is the organization of the meso-
derm, as in the newt or the second chick organizer.
The blastopore is not only the centre of the move-
ments which are going on but also of the formative
influences which are at work.

CHAPTER V
THE ADDITION OF DETAILS

Secondary Organization Centres

After the organization centre has acted in the newt
or chicken embryo, the main outlines of the future
animal are laid down. But the embryo is still very
undeveloped and the outlines have to be filled in
with all the multifarious details of the adult ; none
of the minor organs, such as eyes, ears, lungs, and
legs have yet appeared. Many of these minor organs
are also developed as responses to organizing
stimuli. The organization centres which have been
described so far are, in fact, only the primary
organization centres, and they are succeeded by
secondary ones, and these again by tertiary ones, and
so on. One example of this succession of organization
centres has already been mentioned; in the chick
there is first an organization centre in the endoderm
which induces the primitive streak, which then
becomes an organization centre itself and induces the
neural plate. Many similar examples are known. In
the newt, for instance, the neural plate closes up to
form the neural groove, and the two sides of the
groove eventually join together at the top and cut
off the lower part as a tube sunk below the surface.
From the front end of this tube, two hollow pro-
cesses grow out, which are the beginnings of the two
eyes. When these processes reach the surface and

THE ADDITION OF DETAILS

79

touch the skin, they act as organization centres and
induce the skin to form a lens (Fig. 21). There are
other secondary organization centres which induce
various parts of the embryo to become legs or gills,
etc. We do not always know exactly which sorts of
tissue carry the organizing power, but we find that

BRAIN

SKIN

Fig. 21. — ^The development of the eye in vertebrates. A dia-
grammatic section through the head; the left side shows an
early stage and the right side an older one

if we graft non-presumptive leg material into the
region where the leg will appear, there is something
there which succeeds in turning this tissue into a leg.

Special Factories Making Special Parts

Once the various parts of the embryo have been
started off in definite directions by the organization
centres, they can continue developing on their own.
They are, in fact, capable of self-differentiating. This
does not mean that every single part of the leg, for
instance, has its fate absolutely fixed and can only

80 HOW ANIMALS DEVELOP

develop in one way. It means that if the lump of
presumptive leg tissue develops at all, it will develop
into a leg. But within the lump a good deal of
changing about of various parts can go on without
affecting the result. If a piece is removed the leg-
rudiment will nevertheless be able to form a com-
plete leg. A system like this, where the various parts
can be changed round or taken away without
affecting the result of the subsequent development, is
called by the grand name of a harmonious equipotential
system. As a matter of fact, it is very doubtful if any
completely harmonious equi-potential systems exist.
There are nearly always some differences between the
different parts of the system so that changes of some
kind have no effect but others have. The leg-rudiment
may have a tendency to form a complete leg out of
whatever tissue is available, but the tissue is never
quite labile in every way and therefore, after some
injuries, cannot be moulded into an entire limb. But
the tendency to form a whole leg out of an injured
rudiment suggests that the tissue is, in some way
which we do not yet understand, in equilibrium
when it forms a complete whole. Dragomirov has
recently studied the question in the eyes of the newt
embryo. He cut out and isolated various parts of the
eye rudiment and watched how they returned to the
normal shape. He found that the isolated pieces could
develop in various ways, which represented different
short-cuts, as it were, back to the equilibrium position
of being a complete eye.

Once, when I was working in Germany, I met a

THE ADDITION OF DETAILS 8 1

very enthusiastic Russian embryologist, who was full
of the similarity between the organization centre and
the Communist party. He said that the organizer
arises as a small ordered part of the egg, and when
a revolution happens (that is, gastrulation occurs)
the organizer remains in control because of its own
order and discipline, just like the Communist party
in Russia, according to him. As soon as the main
job is over the party starts a lot of separate factories
going, each to perform some special function, and
these factories are quite self-sufficient within their
own limits and elect their own executives, just as the
secondary organizers and the regions controlled by
them can self-differentiate and act as harmonious
equipotential systems, running their own show with-
out much control from the primary organization
centre. I do not know enough about Russia to say
whether the Communist party really works like that,
but the comparison does bring out some important
features of the way the organizers work.

Once an organ rudiment has been determined
and starts self-differentiating, it is amazing how
fully and in what detail it develops. A very good
example of this is seen if the rudiment of the leg-
bones are removed from a chicken embryo and grown
in a culture, like the cultures used for growing entire
embryos. Miss Fell, collaborating with Dr. Canti,
has made a cinematograph film of what happens,
and the pictures shown in Fig. 22 are taken from this
film. When the rudiment was isolated from the
embryo, it was a little shapeless mass of mesoderm.

82 HOW ANIMALS DEVELOP

From this a well-formed leg had developed, and
the cells had turned into cartilage cells and were
beginning to turn into bone by the time the experi-
ment ended. The ends of the bones at the joints
of the hip and knee had nearly the right shape;
as we shall see later (p. 1 1 1), the actual functioning
of the joints and the movements which take place
there have a certain influence on the shape of
the articulating ends of the bones, but even without
this help the rudiment can develop quite a good joint-
surface. Further, not only did the bone-rudiment
develop its right shape and right sort of cells, but the
various chemical processes which go on in developing
bone also occurred. There is a particular substance
called phosphatase which appears at a certain stage
or normal development and is concerned with the lay-
ing down of the calcium phosphate out of which the
bone is made ; and it was shown that the isolated rudi-
ment had produced this substance at the right time.
Another very remarkable instance of the self-
sufficiency of organ rudiments after they have
become determined is found in the embryonic kidney
or mesonephros of the chicken. This structure only
exists in the embryo and degenerates and falls to
bits before the chick is born. If the rudiment is cut
out and isolated it goes on developing quite normally
for the right length of time and then punctually starts
to degenerate. A similar capacity for independent
development has been found in the organ-rudiments
of frogs and newts and most other animals which
have been investigated.

THE ADDITION OF DETAILS 83

Mosaic Eggs

The stage of development which has just been
described, in which all the different parts of the
embryo arc determined, is called the mosaic stage,
because then each separate part is independent and
self-sufficient like the separate stones in a mosaic. In
most embryos this stage is attained gradually, as the
successive organization centres do their work. The
primary organization centre cuts the embryo up
into a mosaic made up of a few big blocks, the
neural plate and skin, and so on, then the secondary
organizers cut up those blocks into smaller ones, the
eyes, ears, legs, and other organs. But there are
some eggs, to which we have so far paid very little
attention, in which the mosaic stage is reached very
early in development, so that there is no time for us
to perform experiments to find out whether there are
any organization centres or not. In the most extreme
cases the egg is a mosaic immediately after it is
fertilized. In these eggs, of which the Ascidian, or
sea-squirt, egg is one of the best known examples,
we can sometimes show that there are definite sub-
stances each of which is essential for the formation
of some particular organ. They are known as organ-
forming substances. We do not know what they are,
but in the eggs of some species of animals they have
characteristic colours or textures so that they can
be easily recognized. The essential fact about them
is that if they are moved into an abnormal position
in the egg, the particular organ into which they

84 HOW ANIMALS DEVELOP

develop will be found to appear in this abnormal
position : or if one such substance is removed from
the egg altogether, the organ will simply fail to turn
up at all.

If such a mosaic egg is cut in two, each half can only
develop into half an embryo since it only has half
the right organ-forming substances. This is quite
different from the result of Spemann's experiment,
which was mentioned in Chapter 11, where it was
described how he made one egg produce two whole
embryos by constricting it in half with a hair. As a
matter of fact, he was lucky in this particular ex-
periment ; in other cases he sometimes only got one
embryo. Because, after all, the newt's egg has got
one "organ- forming substance" or something very
like one, namely, the organizer. Spemann found
that only those halves which contained the organizer
developed into embryos, and he got one or two
embryos, according as the organizer was included
whole in one half, or cut in two and divided between
the two halves.

Different embryos can be arranged in a complete
series between those which, like the newt, are late at
arriving at the mosaic stage, and those which arrive
early. In the former we can often prove the presence
of an organization centre, but in the latter we cannot
discover whether there is one or not. Of course in
these mosaic eggs there may be an organizer which
acts so early that we cannot find it, and induces the
formation of the organ-forming substances. But it is
impossible to explain all organ-forming substances by

THE ADDITION OF DETAILS 85

saying that they have been induced by organizers,
because, if so, where does the organizer come from?
It is rather the other way about. The ordinary newt
organizer should be regarded as itself very like an
organ-forming substance. Wherever it is, there the
mesoderm develops out of it and the rest of the
embryo is induced ; if it is removed altogether, no
embryo appears. In the frog's tgg we can actually
see the organizer, coloured grey and collected on one
side of the tgg where the blastopore will appear later,
just like an organ-forming substance in an Ascidian's
egg. The organizer must be prepared by chemical
processes going on in the egg and then localized in
one region by the external agents, which were
mentioned earlier (p. 62). We know very little about
the preparatory processes, but we have a very few
hints about one kind of process which must be
involved in the newt.

As we shall see in the next chapter, one of the
important things about the organizer is that it con-
tains an active chemical substance which gives the
ectoderm the necessary stimulus to make it develop
into neural plate. We do not yet know exactly what
the substance is, though we are rapidly finding out.
It is provisionally called the evocator, because it
evokes the formation of the neural plate. Now it has
been shown that an inactive form of the evocator is
present in all adult tissues and, further, that the same
inactive form is distributed throughout the whole
newt's egg. In the organization centre this inactive
form is converted, much earher than elsewhere, into

86 HOW ANIMALS DEVELOP

the active form which is found in the adult tissues.
The preparation of the organizer therefore involves
the activation of a substance. When we know more
about the exact chemical formula of the evocator,
we shall perhaps be able to find out how this
activation happens.

The localization of the organizer, i.e. the deter-
mination of whereabouts in the ogg the activation
shall happen, must be done by factors outside the
egg, partly by the way the egg is formed in the
ovary and, in the frog, at any rate, partly by the
place where the sperm enters the egg in fertilization.
The localization of organ-forming substances in
Ascidians and other mosaic eggs must also be done
by external agents, and here again the same two
factors are probably important.

Human eggs are not mosaic. They probably
develop a primary organization centre which acts at
the stage corresponding to that in which the second
chick organizer is active, that is, at the primitive
streak stage. The embryo reaches this stage about
8 days after conception. Before then, separate
bits which may get split off by chance can develop
into whole embryos if they are big enough. The
most common sort of splitting is for the embryo to
fall into two halves : probably after the egg has
cleaved the first time the two daughter cells fail to
stick together for some reason. We then get identical
twins, which are not the same as fraternal twins, which
arise when two eggs are fertilized simultaneously.
Identical twins must, of course, have exactly the

THE ADDITION OF DETAILS 87

same hereditary factors, and if one can find identical
twins which have been separated in early life and
brought up in different families, one can measure the
relative importance of heredity and upbringing by
finding how much they do or do not resemble each
other. So far only a fairly small number of pairs of
separated identical twins have been carefully studied,
so that the conclusions are not very certain, but, on
the whole, the information which has been collected
emphasizes the importance of heredity, even for
shaping intellectual and emotional qualities.

Some animals have specialized in producing many
embryos from one egg. One species of Armadillo, for
instance, always has four identical quadruplets.
Other animals, like some of the parasitic wasps
which lay eggs in caterpillars of other insects, pro-
duce enormous numbers of young from one egg. In
such cases the egg falls to pieces at an early stage in
its development, and each piece then goes on to make
a whole embryo. We may perhaps find out how it is
done, and then we could control twin production at
will, and produce a large number of babies from an
egg with a particularly good set of hereditary factors.

Different Ways of Building Up Similar Structures

When an embryo reaches the mosaic stage the real
elaboration of detail begins. The ways in which the
different organs are built up are too manifold and
too complicated to be summarized in such a short
book as this. There is only room for a description
of how the main outlines of the animal are laid

88 HOW ANIMALS DEVELOP

down and an idea of the way in which this funda-
mental pattern is called forth. There are many
excellent books, such as MacBride's Invertebrate
Embryology and Graham Kerr's Vertebrate Embryology y
where the details of the later processes of develop-
ment are described. The reader who consults these
books will be amazed at the mass of knowledge we
have about the development of the embryos in
different animal groups.

It has been said above that, as a rule, embryos of
different kinds resemble one another the more the
younger they are. This is not always true as regards
the separate organs. It is very interesting to find that
sometimes distantly related animals have evolved
similar organs, but have evolved them in quite dif-
ferent ways which are recapitulated in their embryo-
logical development. The clearest examples of this
are seen in organs which have to perform some quite
definite function, which more or less dictates their
structure. For instance, an efficient eye must have a
sensitive layer of tissue (the retina) to perceive light,
a lens to focus the light, and an apparatus like an
iris-diaphragm on a camera to regulate the amount
of light which enters. In the higher vertebrates,
such as man, mammals, birds, and newts, the retina
originates from an outgrowth of the neural plate in
the brain region which we have already described. It
induces the formation of a lens from the skin of the
head. The iris is formed from the retina (Fig. 21).
Now all these parts are quite well-developed in the
eyes of octopuses, which belong to the group of

THE ADDITION OF DETAILS

89

animals known as Cephalopods and have hardly any
connection with vertebrates. And we find, if we study
the embryology of octopuses, that their eyes, although
very similar in plan to vertebrate eyes, are developed
in a totally different way (Fig. 23). The whole retina
is made from a patch of skin which sinks inwards and

IRIS

SKIN ^^ '^ LENS

RETINA

Fig. 23. — Development of the eye in the octopus, (a) Is a section

of the hollow ball formed by a fold of the skin, (b) Shows the

retina developed from this fold, and the iris from two more folds,

one on each side of the eye

becomes cut off from the surface, so that it forms a
hollow sunken sphere. Then the lens differentiates
from the thin roof of this sphere, and two circular
folds of skin grow up all round, the inner fold
becoming the iris, while the other may join up
across the top and become transparent and so change
into a cornea, like the vertebrate cornea, which is a
sort of protective eye-glass covering the pupil. The
octopus-brain takes no part in the whole process,
though it does, of course, eventually become con-
nected to the eye by a nerve.

go HOW ANIMALS DEVELOP

Larvae

In many animals the process of development is
complicated by the fact that the animal passes
through one or more larval stages before it becomes
adult. The best known illustration of this is found
in the life-history of insects. Everybody knows that a
butterfly's tgg develops first into a caterpillar and
then into a pupa or chrysalis, and only turns into a
butterfly after all this preparation. Some insects have
a much simpler development; earwigs, for instance,
hatch out of the tgg as little earwigs, which look
quite like the adult, although there are still a few
changes to be made. But a caterpillar is extremely
different from an adult butterfly: so different, in
fact, that nearly all its organs have to be broken
down and absorbed in the chrysalis stage, when they
provide material which nourishes the new organs out
of which the butterfly is built up. For instance, only
the three pairs of legs nearest the head persist into
the adult, and all the others disappear. The wings and
most of the adult organs develop from little lumps
of tissue called imaginal discs which are formed quite
early in the caterpillar and wait till the pupa stage
before they start growing. Fig. 24 shows the front
part of a caterpillar of a swallow-tail butterfly, with
part of the skin lifted up to show the imaginal discs
from which the wings will grow.

Very many invertebrate animals and a few verte-
brates go through larval stages before they become
adult, and there may be a whole series of different

THE ADDrnON OF DETAILS

91

Stages, so that their life-history is very complicated.
These larval stages often represent ancestors in the
evolution of the animals. For instance, frogs were
evolved from ancestors which lived in water, and

Fig. 24. — Part of a caterpillar v/ith the skin dissected away
to show the buds from which the butterfly's wings will arise

they still have a water-living larval stage, the tad-
pole. The Ascidians, which we mentioned before as
examples of animals with mosaic eggs, are not so
well known as frogs, but they also have a larval stage,
which is rather like a tadpole. Here the meta-
morphosis by which the larvae turn into the adult is
much more radical, although the adults remain

92 HOW ANIMALS DEVELOP

aquatic. The tadpoles swim about freely, but the
adults are fixed to the sea-bottom and are simple
sacks, rather like sea-anemones in some ways.
Nearly all trace of their original structure is lost, and
we should hardly have realized that they are near
relations of the vertebrates if we did not know what
the larvae are like.

It is not very obvious why the life-histories of
some animals should be complicated by the develop-
ment of larvae forms when the animals are finally
going to turn round and become something abso-
lutely different. To develop into a butterfly by first
becoming a caterpillar is rather like going to Bir-
mingham by way of Beachy Head, as Chesterton has
it. Probably it serves a useful purpose by making the
embryo able to support itself before its development
is complete, so that there is no need to store so much
yolk in the egg to keep the embryo alive. But to show
why something is useful does not explain how it
arose. The evolution of complicated and specialized
larvae may be a consequence of the competition
between different young embryos for the food which
is suitable to young as opposed to adult creatures. As
soon as embryos start to feed themselves, they will
be submitted to the struggle for existence and must
prove themselves efficient or perish. Just as the same
sort of competition led to the evolution of the adults,
so it would force the embryos or larvae to become
more specialized and complicated.

%«l

^^Hii^^k^' ' -i^^EIRh

BEGINNING OF 1ST DAY

3W) D«r

:^^^^^^^^ "'=^ 1

imdpWT0f Z

4THDAr

2ND DAY

ffflf'^D^''"

Fig. 22. — Self-differentiation of the leg bones of a chick in culture.
(From a cinema film by Canti and Fell.)

Fig. 25. — Whitemoor Marshalling Yard, L.N.E.R.

CHAPTER VI

THE DEVELOPMENT OF PATTERN

How the Organizer Works

The discovery of organization centres is only a
beginning of the analysis of why an embryo develops,
but it is a very promising beginning. It provides some
sort of an answer to the fundamental questions of
embryology, why does a certain part of the embryo
develop into this organ and another part into that?
and how are the parts fitted together? We can already
say why part of the gastrula becomes the neural
plate. It does so because the organization centre
stimulated it to develop in that way. But there are
two reasons why that is not quite the whole of the
story. For one thing, the embryonic tissues can only
react to the stimulus of the organizer when they are
ready to do so. The organizer does not seem to be
able to induce anything in tissue younger than the
early gastrula stage. We do not know why this is,
but probably various chemical processes go on in
the cleavage cells, so that by the time gastrulation
begins they have become reactive and can be
affected by the organizer. When they are reactive,
they are said to be "competent," but the competence
does not last long. After the end of gastrulation the
ectoderm loses it power to form neural plates under
the influence of the organizer. That is to say, it
becomes non-competent again as regards this pro-

94 HOW ANIMALS DEVELOP

cess ; but as we have seen, it acquires other com-
petencies and reacts to other organizers by forming
other organs.

Ahhough we know so little about competence, or
what makes a tissue reactive, we have found out
something about the stimulus which the organizer
provides. It was first found, both in the newt and
the chicken, that the organizer was still effective
after it had been killed, so the stimulus cannot
depend on any property peculiar to living cells.
Quite recently it has been shown that the stimulus
is really due to a chemical substance, but the sub-
stance has not yet been purified and analysed.
When material containing this substance is im-
planted into an embryo, it stimulates the competent
tissue to form an extra, induced, neural plate. But
this neural plate seems to differ in a very interesting
way from those which are induced by lining
organizers. The usual induced neural plate is part
of an embryo, it forms the nervous system of a head
or a tail or part of the trunk (for instance, see the
induced head in Fig. i8). The neural plates induced
by the chemical substance on the other hand seem
to belong to no particular part of the embryo ; they
are just neural plates with no definite shape to show
which part of the embryo they are. If we think about
it, this is what we should expect. Because it is clearly
impossible for a single chemical substance acting on
the competent ectoderm to produce all the different
parts of the neural plate, unless, indeed, the various
parts of the ectoderm differ from one another in

THE DEVELOPMENT OF PATTERN 95

some way, which does not seem to be the case. It
seems, then, that the chemical substance simply gives
the stimulus for the neural plate to be formed and
that something else must be present in the living
organizer to determine which part or parts of the
neural plate it shall be. The chemical stimulus is
called the evocator and the something else which
determines which part of the neural plate shall be
induced is called the individuation field.

The fact that an organization centre contains an
individuation field is the second of the two reasons
why it is not sufficient to say that Spemann's dis-
covery merely tells us why some particular part of
the embryo becomes neural plate. The full statement
is that some of the ectoderm in the gastrula becomes
neural plate because, while it is in a competent
state with respect to this process, it is acted on by the
evocator in the organization centre; and that it
becomes a particular part of the normal neural plate
fitted into the whole embryo because it is within
the individuation field of the organization centre.
The idea of the evocator expresses the way in which
the organizer is active as a determiner, and the idea
of the individuation field emphasises the way in
which it is active as a centre of the organization of
the embryo.

Particular Causes and the General Pattern

It is the individuation field which fits the different
parts of the embryo together to make up one single
complete animal. It determines what part of the

96 HOW ANIMALS DEVELOP

neural plate shall be induced by each part of the
organization centre. It therefore determines where
the secondary organizers like the eye-cup shall
arise, and then their individuation fields determine
where the tertiary organizers appear, and so on.
We cannot yet say how the individuation field gets
its effect, but we can describe what the effect is.
We find that the field is a region where there is a
tendency to build up one complete embryo, and
that if we add any extra material or take any away,
the material which is left will do its best, so to speak,
to turn into one embryo and not one and a bit. The
state of being one embryo seems to be a condition of
equilibrium to which the tissue tends to return.

Perhaps a mechanical analogy will make this
clearer without being, at the same time, too mis-
leading. Think of a big railway sorting yard, like
the one in Fig. 25. You are looking down an incline
called the Hump. The wagons are pushed over the
Hump and go running downhill and are sorted out
by the systems of points into the various sidings.
Now an embryo is in some ways analogous to a set
of trucks sliding down the Hump. The first point,
which you see just in front of the nearest two trucks
in the picture, is the primary organization centre
and shunts off one set of trucks to the left, to become
skin, and another set to the right to become neural
plate. The next set of points are the secondary
organizers, which we discussed in the last chapter,
and they again sort out the neural plate trucks into
brain trucks and spinal column trucks, and the

THE DEVELOPMENT OF PATTERN 97

skin trucks into lens and epidermis trucks. And so
on through all the sets of points, representing all
the organizers, till the final trains are made up
in the sidings, or, as we may say, the final organs are
developed from the embryo.

In this model a competent tissue is analogous to a
truck just approaching a point. According as the
tissue is acted on or not acted on by an organizer, it
develops into this or that, and according as the
truck finds the points this way or the other, so it
runs down this siding or that. But in this com-
parison each point would act as an evocator and not
as an organizer, unless there is something to com-
pare with the individuators of the organizers.
Individuation by the primary organization centre
means determining what detailed structure the in-
duced organ will have, it means settling whether it
will be brain or spinal column, etc. In our model,
therefore, it means sorting a whole set of trucks into
their final sidings so that each siding gets the right
number. The first point, or primary organization
centre, can only do that if it is connected in some
way to all the other points by a system of levers so
that they all work together in a co-ordinated way.
The points alone do not provide a full analogy with
living organization centres, one must bring in the
set of individuating levers.

The important thing to remember in this analogy
is that evocation, or the action of one point, can
happen to one single truck, that is to say, to one
small piece of tissue. But individuation, the har-

gS HOW ANIMALS DEVELOP

monious sorting out of a train of trucks, can only
be seen if there are a lot of trucks, that is to say,
it can only happen to a mass composed of several
different regions of tissue. The essence of individua-
tion is to combine several different parts harmoni-
ously together so as to form a complete organ. If a
piece of a neural tube is induced, whether we
recognize it as a brain or as part of a spinal column,
depends on how the top and sides and bottom are
shaped and fitted together. The actual organizers
we know of always fit the various parts together as
harmoniously as possible. We do not find the walls
of a brain fitted together with the top and bottom
of a spinal column. This tendency to make a complete
unit is the most important characteristic properties
of the individuation field, as opposed to the evocator.
There is one other possibility which is also well
expressed in this analogy. In the real sorting yard,
the building up of the right trains is not done by a
set of compensating levers, such as we have imagined
to account for individuation, but instead it is done
by a man sitting in the control-box and using his
brains. Many authors, the most famous of whom is
Driesch, have suggested that we cannot imagine any
material compensating system in the embryo which
would be efficient, but must postulate a non-
material agency which works just like the man in
the control tower. This agency is called an entelechy
and is supposed to be responsible for the harmonious
development of the different parts of the embryo.
It is non-material and cannot be directly discovered

THE DEVELOPMENT OF PATTERN 99

by experiments. It is not supposed to have any con-
nection with the religious or moral soul, but it is a
sort of developmental soul. A hypothesis like this is
in the first place a confession that w^e do not under-
stand how the harmony of development is brought
about, but more than that, it denies that we shall
ever find out. It is frankly defeatist, and on those
grounds alone it is usually discounted by scientists
at the present day, who feel that, although they do
not understand all about development yet, they
still have no grounds for saying that they never will
understand it in the future. Moreover, the organizers
have an easier job than the pointsman in a shunting
yard, because in any one kind of embryo the final
state is fixed. It is as though there was always the
same set of trains to be made up in the final sidings.
The organizers have only to deal with variations in
the raw material, while the pointsman has as well
to build up different sets of trains on different days.
The living newt organization centre therefore does
two things, it evocates a neural plate from the
gastrula ectoderm, and then it individuates itself and
the neural plate and its surroundings generally into
a complete embryo, or as big a part of one as pos-
sible. And we can separate these two processes by
using dead organizers, which evocate but do not
individuate. Some of the other organization centres
we know of seem only to individuate. This is so
with the sea-urchin centre discovered by Horstadius ;
wherever the small vegetative cells are placed they
try to build up a whole embryo. Perhaps Seidel's

100 HOW ANIMALS DEVELOP

activation centre in the dragon-fly can be regarded
as an organization centre which evocates but does
not individuate, whereas the differentiation centre
does individuate.

Regeneration

In many animals individuation fields persist all
through life. Their effect is seen when such an
animal is badly wounded, loses a leg, for example.
The stump of the leg completes itself and builds up
a complete leg again by regenerating the part which
has been lost. In this regeneration the processes
which go on are often very similar to those con-
nected with organization centres in earlier embryonic
life. For instance, if an adult newt loses a leg, a little
cap of cells called the regeneration bud grows on the
end of the stump. The regeneration bud is simply a
little bit of competent tissue, and the individuation
field controls it so that the lost part of the leg
develops out of it. It is not only competent to form
legs but can turn into other things if necessary. If it
is taken off and grafted on to the stump from which
part of the tail has been cut, the tail individuation
field now uses the bit of competent tissue to com-
plete itself, and the regeneration bud, instead of
becoming part of the leg, becomes part of the tail.
In many of the lower organisms, all the tissues
seem to be permanently in a competent state, but
they are normally held together as a complete indi-
vidual in an equilibrium which is determined with
respect to some particular part, which is usually the

THE DEVELOPMENT OF PATTERN lOI

head. If the animal grows so big that part of it gets
out of range of the head's influence, this part may
develop on its own into a whole new animal, and we
thus get the well-known phenomenon of reproduction
by budding, which happens in corals, for instance.
Or if the head is cut out of one animal and grafted
into another some distance away from the host's
head, it can overcome the influence of the host's
head and start to build the competent tissues in
its surroundings into a complete new animal. These
facts can be very easily described in terms of the
hypothesis that there is a gradient of something
along the main axis of the animals, with the head to
the top end of the gradient and the tail at the bottom.
The hypothesis suggests that when any part of the
gradient is isolated from the rest it tends to change
itself back into the whole arrangement, and the head
or top end is particularly well able to do this because
it can alter any lower part which may be in its
neighbourhood so as to bring that part into con-
formity with itself. Gradients of this kind are called
Axial Gradients, and attention was first drawn to their
importance by Child. They may perhaps always
occur in individuation fields in some form or other.
But until we know rather more about what they arc
gradients of, they must be regarded more as a
descriptive convenience than as a real explanation.

CHAPTER VII
THE FINAL ADJUSTMENTS

The development of an animal is not finished as
soon as all its organs have appeared. The details of
its structure must still be fitted together and adjusted
to one another. Organs like the heart, which are
required early in embryonic life, get a start on
other less necessary parts and are disproportionately
large in the young embryo. The control system of
nerves has to be connected up. Particular parts may
have to be enlarged to meet special demands made
on them. In this chapter some of the ways in which
the final ^'tuning" is carried out will be briefly
described.

How Embryos are Fed

The embryo has to be provided with food until it is
old enough to catch and eat its own nourishment.
The study of the food-supplies of embryos, and the
changes by which the food is digested and then
built up into the tissues of the growing animal, is a
very complicated one. Until recently the whole sub-
ject was a chaos of unrelated facts, but a few years
ago Needham brought together all the scattered
pieces of information in a work entitled Chemical
Embryology and stated the general principles which
emerged. In this book we are mainly concerned with
the development of animal shape, and there will only

THE FINAL ADJUSTMENTS IO3

be space for a short outline of the most important
results of the chemical study of embryos. The most
interesting point of view from which to consider the
question is that of evolutionary adaptation ; the dif-
ferent environments in which animals live make
different demands which must be satisfied by
animals which live in them.

The sea, where life first evolved, does not provide
many of the substances necessary for a developing
egg. These substances are (i) oxygen, (2) water,
(3) inorganic salts, (4) carbohydrates, like sugar,
which can be burnt to provide energy, (5) fats, also
mainly for fuel, (6) proteins, which are the real
**flesh-forming" substances. Of these the sea provides
the first three. The others have to be supplied to
the embryo in the yolk. But the sea abounds in very
small living creatures which provide suitable food for
quite tiny larvae, so that the amount of yolk need
only suffice for the earliest stages of development.

The freshwater environment does not contain
enough salts to be absorbed by the embryo, and it
therefore can only be inhabited by creatures which
provide sufficient salts in the egg. But the most
difficult evolutionary step, from the embryological
as from every other point of view, must have been
the conquest of dry land. Here there is no useful
substance, except oxygen, which can be absorbed
from outside, and the embryo has to be provided
not only with its organic materials and salts but also
with its water. Amphibia, which are the most
primitive land animals, have, as a matter of fact,

104 HOW ANIMALS DEVELOP

failed in the last respect, and must return to water
to breed since their embryos would otherwise dry
up. The first true land animals were the reptiles.
They and their descendants, the birds, are quite
independent of water for breeding, as they have
evolved the device of enclosing the egg in an im-
permeable membrane which does not allow the
moisture to escape, although it allows gases such as
oxygen to be absorbed. Some of the intermediate
stages in this evolutionary advance have still sur-
vived ; for instance, one sort of turtle lays eggs with
a rather soft and permeable covering, which can
only develop if they are deposited in wet sand ; the
turtle scrapes a hole in the sand, lays the eggs, and
then urinates over them to moisten them.

The closed-box, or "cleidoic" egg^ although it
solves the drought problem fairly satisfactorily, is
only workable if several other requirements are ful-
filled. The most important of these concerns the
waste products, of which the embryo, like all other
animals, has to rid itself. One waste product is
carbon-dioxide, which is gaseous and can be allowed
to diffuse out through the shell. The other main type
of waste is the nitrogenous matter derived from the
breakdown of proteins. Water-living embryos turn
this into ammonia which diffuses out into the sur-
rounding water. But it would not diffuse away so
readily from a closed-box egg and would accumulate
to such an extent that it would be dangerous. The
closed-box animals have therefore had to evolve
another method of getting rid of their nitrogenous

THE FINAL ADJUSTMENTS IO5

waste products. What they actually do is to convert
the nitrogen into fairly insoluble substances, such
as urea, or, in some highly evolved animals, aric
acid, which is kept in a special organ until the
embryo escapes from the shell and can excrete it.
In the development of birds, for instance, there is a
very striking example of chemical recapitulation in
this respect; in the early stages the nitrogen is
excreted as ammonia, as it is in fish, then it is con-
verted into urea and finally, at the end of develop-
ment, most of the waste nitrogen is being formed into
uric acid. Birds and reptiles have also become
modified to produce less nitrogenous waste ; they do
this by using more fat and carbohydrate and less
protein, as fuel, and they get the added advantage
from this that the fat and carbohydrate give rise to
some water when burned and thus help with the
provision of the necessary moisture.

So far nothing has been said about the feeding of
the mammalian embryo. This is because of the quite
special and peculiar conditions which are involved
in uterine life. In a sense, the mammals have found
a way of returning their embryos to the sea, the
"sea" in this case being the maternal blood, which
can supply oxygen, water, and salts, and can remove
waste products, and which has the additional
advantage of supplying carbohydrates, fats, and
proteins as well.

The essential feature of the evolutionary step taken
by the mammals is to place the embryo inside the
body of the mother and to bring the embryonic and

I06 HOW ANIMALS DEVELOP

maternal blood circulations into close contact. In
some other animals, for instance, some kinds of fish,
the embryo develops for some time within its
mother's body, but it is only in the mammals that
the connection of the two blood streams is at all
intimate. Even in mammals maternal blood never
circulates actually through the embryonic blood-
vessels. If it did, not only might the mother's female
sex hormones disturb the development of the sex of
her sons, but the embryo would actually be killed by
the foreign proteins, since each animal has a chemical
individuality which has to be respected. There is
therefore always a filter between the maternal blood
and the embryo. This filter is the placenta, which is
developed from the trophoblast, or non-embryonic
part of the embryo which was described above. The
trophoblast Hes against the wall of the uterus, and
substances which pass from the mother into the
embryo have to pass through the fining of the
uterine blood-vessel, through the connective tissue
surrounding it, through the wall of the uterus, then
into the embryonic circulation through the wall of
the placenta, through connective tissue, and finally
the lining of the embryonic blood-vessel. There are
thus six layers to be passed through (Fig. 26, a). But
these conditions only hold in the most primitive
types of placenta ; they are found, for instance, in
the pig and the cow. In some other mammals the
passage of substances is made easier by the disap-
pearance of some or all of the maternal layers. In
the stag the maternal wall of the uterus disappears

THE FINAL ADJUSTMENTS

107

over large areas, in the cat the uterine connective
tissue goes, and in mice, rabbits, and men the walls

E C

Fig. 26. — The different types of placenta. The part derived from the
embryo is above, and that derived from the mother below in each
figure. {A) The lining of the embryonic blood-vessel. {B) Embryonic
connective tissue. (C) Embryonic membrane. (D) Maternal mem-
brane. {E) Maternal connective tissue. (F) Lining of maternal blood-
vessel. In {a), which is the least developed type, all six layers are
present. In (b), layer (C) lies against {E) in the folds. In (c), (D) has
disappeared entirely and (C) lies against (F). In {d) (man), (C) lies
against the maternal blood itself. {UM) is the uterine milk in (a) and {b)

of the uterine blood-vessels break down and the
maternal blood lies right against the wall of the
placenta, and there are only three layers left separat-
ing it from the embryonic blood. In the same series
of animals the wall of the placenta becomes more

I08 HOW ANIMALS DEVELOP

and more folded so as to increase the area over which
the absorption of food can take place. In man the
placental wall forms thin branching fingers, con-
taining blood-vessels, which dip down into pools of
maternal blood left by the breakdown of the uterine
blood-vessels.

Most of the embryo's food passes into its blood
stream through the placenta, but the process is not
really a simple filtration. The wall of the placenta,
or trophoblast, breaks down the proteins offered to
it by the maternal blood and passes them on to the
embryo in a digested form ready to be built up
again into the particular substances which the
embryo requires for its growing organs. At the same
time the placenta passes back to the mother the
waste products of which the embryo has to rid itself;
in the more elaborate types of placenta this back-
ward passage is so efficient that the embryo never
develops a functional embryonic kidney, which other
embryos have evolved to deal with their excretion
before the final adult kidney is ready.

Not quite all the embryo's food comes from the
mother's blood. Some is provided by the so-called
uterine milk, which is secreted by glands in the
uterus, chiefly in animals with simple placentas.
In the more complicated types, the embryo derives
a certain amount of nourishment from the maternal
tissues — the wall of the uterus, the connective
tissue and the lining of the blood-vessels — ^which it
digests and absorbs. This process goes on particularly
rapidly in early stages of development. In man,

THE FINAL ADJUSTMENTS IO9

young embryos are very difficult to find, and as yet
no stage is known which has not burrowed into the
side of the uterus, digesting the maternal tissue so
as to prepare a space in which to develop embedded
in its mother's flesh. The embryo must start on this
cannibal existence almost immediately after it is
fertilized. In fact, the connection between the
embryo and its mother is so highly developed and
specialized in Man that no further evolution along
these lines seems conceivable.

It is often the failure of such a specialized organ to
be able to evolve to meet new conditions which leads
to the extinction of a species, and some authors have
suggested that Man may eventually die out because
of the over-specialization of his placenta.

Growth

Many animals never stop developing their whole
life long. It is only for convenience that we say that
a man becomes adult at the age of twenty-one. And
similarly with other animals, there is often no point at
which we can say definitely that the period of change
is over. This is particularly the case with animals
which go on growing throughout their whole
existence. With others, such as butterflies, once the
pupa has metamorphosed into a butterfly, no more
change is possible, and there can be no objection to
calling the animal adult. All animals which grow,
change not only in absolute size, but also in pro-
portions and therefore in shape. This alteration is
most rapid, of course, in the early years of life and

no

HOW ANIMALS DEVELOP

gets slower and slower as the animal gets older.
Fig. 27 shows how much the proportions alter as a
baby grows up to be a man. There is often an
evolutionary significance in these changes of pro-
portion and we can show, in the evolutionary tree of

Fig. 27. — The changes of proportion during growth, (a) and {c) are
human and gorilla foetuses, {b) and (d) an adult man and gorilla.
All the figures are adjusted to have the same sitting height. Notice
that in man the upper part of the body retains more nearly the foetal
proportions, whereas in the gorilla the legs remain more unchanged
while the head, and particularly the brain-case, becomes very small.

(After Schultz.)

the horses, for instance, which we know from fossils,
how one species has changed into another by an
alteration of the rates of growth in different direc-
tions. Professor Huxley has recently written a
fascinating book on this subject called Problems of
Relative Growth.

The rates of growth of the different parts of a
young animal or embryo at any given stage are not
quite rigidly fixed, but can be altered for two

THE FINAL ADJUSTMENTS III

reasons : either so as to fit in with its surroundings,
or in response to the amount of work the part has
to do. An alteration due to the first reason is seen if
a small lens is grafted into a large eye: the small
lens grows faster than it normally would and the
large eye more slowly, so that together they make
up a harmonious but middle-sized organ. The in-
fluence of the second factor, the amount of work
required, is shown by a comparison of tadpoles
which have been reared on a rich diet of animal
matter with those reared on a poorer vegetable diet.
The gut of the vegetarian tadpole has to work
harder to absorb enough nourishment from its
poorer food and grows much longer than that of the
flesh-eating tadpoles (Fig. 28).

The Influence of Function

The work which an organ has to do and the move-
ments it makes may influence not only its size but
also its structure. There is a very good example of
this in the differentiation of the leg-bones of the
chick. It was found that the isolated thigh-bone
can produce quite a well-shaped end to fit into
the knee-joint even when it is lying in a culture
with no muscles attached to it and makes no move-
ments at all. If a thigh- and shin-bone are grown
together in this way, both sides of the joint begin to
form, but soon the two bones fuse together and the
joint becomes obliterated. If, on the other hand, the
two bones are exercised (by waggling them by hand),
the joint goes on developing properly. Thus move-

112

HOW ANIMALS DEVELOP

merit seems to be very important for the development
of a really satisfactory joint.

The movements which developing embryos make
are not the only functional factors which have im-

m

Fig. 28. — Differences in the guts of tadpoles fed (a) mainly
on vegetables, (b) exclusively on meat. (From Diirken.)

portant effects on development. Sometimes a develop-
ing structure is put under tension because it is pulled
out by its rapidly growing surroundings. Such ten-
sions are probably very important, because if any-
thing is stretched, any minute particles within it
tend to become orientated parallel to the direction
of stretching. Now it seems that the spaces in the
embryo are sometimes filled with a jelly-like sub-
stance which is made up of little elongated particles
which get orientated in various ways under the

THE FINAL ADJUSTMENTS II3

tensions set up in the developing embryo. Many
processes of development involve the movement of
cells from one place to another inside the embryo,
and we know that cells will often move along lines
of orientated particles. In this way the tensions may
lay down the paths followed by the streams of cells
and thus determine where they arrive.

The Nervous System and Development

The nervous system, which is so important for the
integration of the adult body, might be expected to
play an important part in enabling the embryo to
develop harmoniously. Actually it has been found to
be less effective in this particular respect than one
might suppose, but many other interesting points
arise about it. Before the nervous system can integrate
the parts of the body, the nerves must grow out
from the neural tube and reach the organs which they
finally innervate. While the nerves are growing the
paths along which they move are fixed by the posi-
tions of the organs to which they will become
attached. If a limb-rudiment is cut out of its normal
situation and grafted a short distance away, the
nerves bend out of their usual course to follow it.
The developing leg seems to attract them. This
attraction can be exerted by most sorts of developing
tissue, and if a leg is cut off and a nose grafted
nearby, the leg nerve fibres cheerfully grow off
towards the nose. But the actual way in which the
nerve joins on to the leg muscles or the nose is
another matter, and is more rigidly fixed.

114 ^^^ ANIMALS DEVELOP

Once the nerve fibres have got to their destination
and become attached, there is a mutual interaction
between the nerve and the organ. If the organ is
made smaller than normal in any way or is removed
altogether, the number of sensory nerve fibres
coming back from it carrying sensations up the
spinal column to the brain is reduced, although the
number of motor nerve fibres going down the spinal
column to carry orders to the organ is not affected.
On the other hand, the nerve sometimes affects
the organ ; thus it is usually impossible for an organ
to regenerate if the nerve is cut. In view of this
dependence of regeneration on the presence of
nerves, it is surprising to find that nerves are quite
unnecessary for ordinary embryonic development,
and that it is possible to prevent any nerves at all
from growing into a leg-rudiment without this
having any very great effect in the development of
the leg, except that the muscles, although well
formed, do not function and therefore do not grow
as large as usual.

Hormones

Much of the integration of the developing animal
seems in fact to be done not by the nervous system
but by substances circulating in the blood-stream. It
is usual to call these substances hormones, but it is
difficult to give an exact definition of this term. They
are usually thought of as substances which are
present in the blood in very small quantities and
which have a specific effect on various organs, but,

Fig. 29. — Effects of the pituitary gland, (a) Giant

with over-developed pituitary. (From Engelbach.)

{b) Dwarf with under-developed pituitary. (From

Behrens and Barr.)

Fig. 30. — Comparison of the faces of various sorts of dogs with
those of men suffering from hormone diseases. (From Stockard.)

THE FINAL ADJUSTMENTS I 1 5

as we shall see, some of these effects can be brought
about by other non-specific substances. The hor-
mones are usually manufactured in special organs
set aside in the body for that purpose, which are
called the ductless glands, because they have no
opening to the exterior of the body but pour out
the substances they make directly into the blood-
stream. The ductless glands have all sorts of different
origins in development. For instance, the pineal
gland in man is formed from a structure which in
our remote ancestors was a third eye situated on top
of the head, and in its embryonic development traces
of this ancestry can still be found. One of the most
interesting of the glands is the pituitary, which is
built up partly from the ectoderm of the mouth
region and partly from the floor of the brain. It lies
well hidden in the skull, underneath the brain, and
seems to manufacture several different substances,
all of which are very active and important. One of
these substances has a great effect on growth. If it is
produced in too small quantities in a child, that
child becomes a dwarf, whereas if it is produced in
too large amounts, the child becomes a giant
(Fig. 29). Sometimes it is only in adult life that the
gland starts to produce too much of the growth-
controlling hormone, and then the main effects are
seen in the face, hands, and feet, all of which become
very large and coarse, giving the condition known
as acromegaly. Other effects of abnormal amounts of
hormones are shown in Fig. 30.

Hormones play an important part in animals

Il6 HOW ANIMALS DEVELOP

which pass through a larval stage. In the frog it has
been shown that it is a hormone which makes the
tadpole metamorphose into an adult frog. The
hormone in question is produced by the thyroid
gland, which lies in the neck in man, and gives rise
to a form of goitre if it becomes too big. It is interest-
ing to find that human thyroid hormone can be
effective in causing metamorphosis in frogs, so the
hormones are not special for each species of animal.
It is probable that the moulting and metamorphosis
of insects is also controlled by hormones, but so far
no vertebrate hormone has been found which will
produce the effects.

The chemical constitutions of some of the hormones
have already been worked out, and the extraordinary
fact has been discovered that it is sometimes possible
to substitute for a natural hormone various other
substances which are chemically rather unlike it.
Perhaps the most striking example is in one of the
numerous hormones concerned with regulating the
development of the sexual organs. A whole series of
substances are known which can be substituted for
this hormone, which is called oestrin. All these sub-
stances have certain points in common, although
they are quite dissimilar in other details. Moreover
some of them can do quite other things ; some can
act like the vitamin D, in preventing animals getting
rickets ; some of them can cause cancer to develop
if they are painted on to the skin constantly for
months; and some of them can actually act as
evocator-substances and cause the induction of

THE FINAL ADJUSTMENTS I17

neural tubes in newt embryos. It seems as if they
were a group of skeleton keys each of which can
unlock several different doors.

Sex

The development of sex is interesting not only in a
general way, because sex is such an important ele-
ment in our make-up, but also from the strictly
embryological point of view it raises quite special
and remarkable problems. When an animal develops,
not only must the sex-cells, eggs and sperm, be
elaborated, but the animal assumes a particular
sexual character which affects its whole constitution,
making it either male or female. These two phases
of sexuality are to some extent distinct, at least in
the way they arise.

The most prominent fact about the sex-cells is that
they are capable of starting off a new development
into another organism. One fertilized egg produces,
among other things, another egg which can be
fertilized and so on ad infinitum. This behaviour was
emphasized in the Theory of the Germ-Track, which
states that there is a continuous succession of germ-
cells, the later ones derived from the earlier ones by
division and reunion in fertilization, so that they are
really all parts of the same living substance. This
line of germ-cells represents, then, an immortal piece
of living matter, which may increase in size but
need never die. The thing which does die is the
individual animal body which the germ-cells make
to provide themselves with a temporary house.

Il8 HOW ANIMALS DEVELOP

One can only make a rigid distinction of this kind
between the temporary body and the immortal
germ-cells if one can show that the germ-cells are
never really a true part of the body but are always
fundamentally separate from it. Now in many cases
it is probably true that the germ-cells never do
belong to the body in any sense except that of just
being inside it. We find, for instance, that at the very
beginning of development there may be a particular
part of the tgg which looks unlike the rest and is set
apart to become the germ-cells ; in such cases there
is, in fact, an organ-forming substance for germ-cells,
and the rigid distinction between body and germ-
cells may be plausible. But often no such substance
can be found, and the germ-cells are probably
formed in the same way as the other differentiated
cells in the body, that is, in response to some
organizer. In this sort of embryo the germ-cells
really act like a part of the body and not as though
they were inhabiting it and did not belong to it.

Then again, it is not only the germ-cells which are
potentially immortal. All young embryonic cells are,
and probably even the highly specialized cells in the
different organs of an adult animal could remain
alive almost indefinitely even although they might
not be able to grow and divide. It is the animal as a
whole which dies, not the individual cells of which
it is made. The immortality of the cells can be
realized by removing them from the body and
growing them in a nutritive medium in culture, like
the embryos mentioned in Chapter m. Anyone

THE FINAL ADJUSTMENTS II9

who wishes to can now make certain of the im-
mortaUty of part of himself as an actual material
living thing by endowing a staff of experts to keep
the cultures going. Each culture, of course, only con-
tains a very small piece of tissue, a few hundredths
of an inch across, so that it is only rather a piecemeal
immortality which science offers. But at the same
time each of these little cultures is growing, doubling
its volume in 2 days, and the tip of your little
finger would grow to the size of the world in
less than 6 months.

We must now turn to the second question; what
decides whether the germ-cells, and the whole
animal, shall be male or female? Actually two groups
of factors work together in this sex-determination,
and sometimes one is the more important, sometimes
the other. One set of factors are given by the heredi-
tary make-up of the embryo and the other set are
particular conditions which arise during develop-
ment. The hereditary basis is probably always
present even where its influence is overcome by the
factors which arise later. The important thing to
notice about the hereditary determination of sex is
that all animals inherit tendencies towards both
maleness and femaleness, sometimes with one pre-
ponderating, sometimes with the other. The heredi-
tary factors or genes for maleness and femaleness are
usually carried on different chromosomes. One
scheme is to have all the genes for one kind of
sexuality, say femaleness, carried on one pair of
chromosomes, which are then called the X-

I20 HOW ANIMALS DEVELOP

chromosomes, while the factors for maleness are
carried on the other pairs, which we can call the A
pairs to distinguish them. Then the sex which
actually develops in an animal depends on the pro-
portion between the Xs and the As, and we find
that a special mechanism is evolved to regulate this
proportion. Thus if the Xs are the female-bearing
chromosomes, a female animal is found to have two
Xs, making a normal chromosome pair, while the
males have only one X, the other X being either
completely absent or represented by a special
* 'empty" Y chromosome, which does not carry any
sex factors. The females therefore have a proportion
of two Xs to the set of As, while the males have one
X to the set of As. This plan makes certain that in
the next generation the males and females will be
about equal in number. All the eggs must contain
one X and one of each of the A pairs, but the sperm
will half of them contain an X and half no X (or a
Y if the animal belongs to a kind which has them).
In fertilization there will be equal numbers of
animals which get an X in both the egg and the
sperm and of animals which get only an X from the
egg and none from the sperm. The first kind will
be females and the second kind males. Sometimes,
however, something goes wrong and the chromo-
somes do not divide properly when the eggs and
sperm are formed, and in this way animals may get
too many Xs in proportion to their As, when they
develop into so-called "super-females," or again
there may be too few Xs when we get "super-

THE FINAL ADJUSTMENTS 121

males" ; and finally we may get proportions inter-
mediate between one X and two Xs to the set of As
and then intermediate forms or ''intersexes" develop.
Again, there are strong and weak varieties of the
male and female factors, and unbalanced inter-
mediate animals can result from some combinations
of them. Most of these abnormalities have been
found in insects, though they may perhaps occur in
other groups where they have not yet been dis-
covered. They are nearly all infertile and generally
feeble.

The sex genes probably work by producing special
sex substances or hormones, and if a young embryo
comes in contact with these substances before its
own sex genes have had time to act, the substances
may get in first and overcome the genes. Or again,
the two influences may act antagonistically and
produce intermediate or intersexual animals. Even
in adult life the sex hormones can produce very
important effects. By various experimental methods
it has been possible to bring about the complete
reversal of sex in some animals, so that, for instance,
a hen which can lay eggs may be changed into
a cock which is functional as a male. The inter-
action of the hereditary sex factors and those which
arise during development obviously can lead to very
complicated results, and there is no space here to
discuss the matter at all fully. Those who wish
to go more deeply into the matter should read
Professor Crew's book, The Genetics of Sexuality in
Animals,

122 HOW ANIMALS DEVELOP

The Activity of Genes in Development

Finally, now that we have got an idea of how devel-
opment comes about, we must ^o back to the question
which was raised in Chapter 2. How do the hereditary
factors or genes affect development? The first point to
emphasise is the enormous importance of their effects.
No animal can develop any characteristic for which it
has not got the hereditary potentialities. The nature
of its genes, which it inherited from its mother and
father, determine all the possible things it may develop
into. Which of these potentialities will be actually
realised as development proceeds depends, of course,
to some extent on the external circumstances or en-
vironment, but in general the influence of the environ-
ment only becomes important in affecting characters
which are developed relatively late in the individual's
lifetime. Human personality and ability are, for in-r
stance, strongly influenced by environment in upbring-
ing, because these are characters which are moulded
at a comparatively late stage, after birth, but whether
a man develops five fingers or four is very little affected
by the environment. It sometimes occurs, for reasons
of grave illness of the mother or other mishaps, that
conditions in the maternal uterus are so unfavourable
that a potentially normal child develops with some
anatomical abnormality of this kind, but this is a
relatively rare occurrence. In general, the characters
which are produced in the early stages of development
are almost entirely determined by the genes, with only

THE FINAL ADJUSTMENTS 123

a relatively minor influence of the external circum-
stances.

It may be asked whether the organ-forming sub-
stances, which we mentioned when discussing mosaic
eggs, or the various gradients which we spoke of in the
eggs of newts and sea urchins, do not play at least as
important a part in determining development as the
genes themselves. If we think only of a single lifetime
they undoubtedly do. In a newt's egg, for instance, the
organiser is located at a particular place, related to the
gradient of yolk. The same is true of the various im-
portant regions we mentioned in insect eggs. But there
are two further points which we must remember.
Firstly, these various centres only become active when
a nucleus has passed into them, that is to say, when the
region of the egg can interact with genes in the nucleus
(see page 77). Secondly, we have to ask, how do these
regions of the egg become located in the right place?
The egg is a cell built up in the ovary of the mother's
body, where it undergoes, as we saw, a long period of
maturation and growth. Now during this period of
maturation the egg is influenced by the genes which
it contains: before the reduction division these are the
same as the genes in any other cell in the mother's
body.

In organisms which have been thoroughly studied
we know many examples of genes whose most impor-
tant effect is to influence the process of egg matura-
tion; usually they lead to the formation of imperfect
eggs which fail to develop, so that they cause the female

124 HOW ANIMALS DEVELOP

in question to be sterile. However, we know of some
genes which allow eggs to be produced, but affect them
in such a way that they always develop into individuals
with a peculiar characteristic. One of the most famous
examples is in a variety of water snail in which some
individuals are coiled in a left-handed screw and others
in a right-handed. This difference depends on the type
of egg which a given mother produces. That in its
turn is determined by the genes which she contains.
We see, then, that the arrangement of the various
regions of the egg, which plays such an important role
in development, is itself the result of the action of
genes in the previous generation.

It is interesting to enquire what happens when an
organiser with one genetic constitution acts on com-
petent cells which have a different constitution. Ex-
periment shows that cells which react to an organiser
can only do so by expressing one or other of the
hereditary potentialities which they contain. It is, in
fact, their own genes which determine the range of
characters they can develop into. All an organiser can
achieve is to select one or other out of this range of
possibilities. ^

What is it that genes are doing that gives them such
overwhelming importance in development? To answer
this we need to decide first of all what actually hap-
pens in development. Now the study of living mate-
rials has led us more and more to the conclusion that
by far the most important constituents of cells are the
proteins. Nearly all the chemical reactions which go

THE FINAL ADJUSTMENTS 125

on in living cells are carried out with the aid of en-
zymes, and these enzymes seem always to be proteins.
There are, of course, many other classes of compounds
in living cells, for instance, lipids (i.e. fats and oils of
various kinds), carbohydrates and many other complex
organic substances; but there are many reasons which
make it seem reasonable to suppose that all these sub-
stances are secondary consequences of the actions of
protein enzymes. This cannot yet be definitely proved,
but most biologists at present adopt as a working hy-
pothesis the idea that the primary action of a gene is
to cause the production of some particular protein
which may act as an enzyme and therefore lead even-
tually to the elaboration of various other types of sub-
stance of the kinds just mentioned.

In the last few years a great deal of the attention of
people interested in development has been concen-
trated on trying to understand the mechanisms by
which genes are able to control the formation of par-
ticular proteins. Very great advances have been made
in this, and we can now say that we have at least an
outline of the answer. Although the problem is essen-
tially an embryological one, the answer to it has not
been found, in the main, by studies on embryos, but
by a converging attack along a number of lines which
at first sight do not seem at all closely related to em-
bryonic development. Some major contributions, for
instance, have come from the study of heredity in
micro-organisms such as bacteria and viruses. Another
important line of evidence has been the X-ray crystal-

126 HOW ANIMALS DEVELOP

lography of certain complicated organic compounds.
A third has been the use of such modern technical
devices as the electron microscope, the ultra-centrifuge,
and radioactive isotopes. The whole story is a very
good example of the way in which different parts of
science can come together and reinforce one another.
When two similar chromosomes are paired together
in a primordial germ cell, as we described on page 30,
they sometimes break at corresponding places and the
two pieces rejoin in the wrong order, so that what had
been the end of chromosome 2 has now become joined
to the beginning of chromosome 1, and vice versa. A
study of this process, which is known as recombina-
tion, has always been one of the most powerful tools
in genetics. It is easy to see that if two genes lie on a
chromosome and are quite a long distance apart,
breakage and rejoining is quite likely to occur between
them, whereas if they lie very close together the chance
of this happening in that particular stretch of chromo-
some is much less. We can therefore discover how far
apart two genes are by determining how often the
recombination happens between them. One of the
most important pieces of recent evidence about the
nature of genes came to light when it became possible
to study recombinations which happen excessively
rarely. Bacteria and viruses are such small organisms
that they can be cultivated in millions or even billions.
A study of their genetics, of course, involves many
highly elaborate techniques, but when these were
eventually worked out it became possible to look for

THE FINAL ADJUSTMENTS 127

recombinations occurring in sections of chromosome
which were so short that a breakage and rejoining
would only occur in that place with a frequency of,
say, once in a million. If we can find that there are two
hereditary factors with recognisably different effects,
lying so near together that recombination between
them happens only once in a million times, we can
from this deduce something about the minimum size
of the units out of which the chromosome is built. It
turned out, in fact, that the size of the units from
which the hereditary material is made is about that of
a moderate-sized organic chemical molecule.

The next step in the argument is to determine what
sort of chemical compounds are present in the chromo-
somes. In fact there are two: proteins and another class
of compounds known as nucleic acids. Which of these
two is the more important, or are they perhaps both
equally important? Since proteins are, as we have seen,
essential for so much of the lif^ of the cell, it might be
thought at first that they would play the essential
role in heredity also, but the evidence is actually on
the other side. In experiments with bacteria it has
been possible to transfer a hereditary characteristic
from one strain to another by using a pure preparation
of nucleic acids, but it has never been possible to do
this by using pure proteins. It seems then that it is the
nucleic acid which is the important constituent of the
chromosome in determining its hereditary effect.

Nucleic acids are made up of a long sequence of rela-
tively small molecules (known as nucleotides) which

128 HOW ANIMALS DEVELOP

are linked together end to end to form a chain. The
evidence about this comes largely from X-ray crystal-
lography. This shows that the type of nucleic acid
found in chromosomes (known as deoxyribose nucleic
acid, or DNA for short) has actually a slightly more
complicated structure than that just described. It con-
sists not of one sequence of nucleotides joined together
as a thread, but of two such threads wound round
each other in a spiral. However, these two intertwined
threads are closely related in their chemical composi-
tion; if, at a particular place in one thread, there is a
given constituent molecule or nucleotide, this imme-
diately determines the nature of the nucleotide at the
corresponding place in the other thread. Thus the
DNA, which we think to be the essential hereditary
substance, consists of a double thread built up from
pairs of nucleotides.

This fits perfectly with the evidence from recombi-
nation which we discussed in the paragraph above.
The pairs of nucleotides which, according to the crys-
tallographers, are the units out of which the DNA
is built, are just about the same size as the smallest
stretches of chromosome which can be detected by
studying the recombination of hereditary factors. The
two stories dovetail together perfectly to give a coher-
ent picture.

Now we have to go on to consider how this thread
of DNA produces a particular protein in the rest of
the cell. The first point is that proteins also, like
nucleic acids, are essentially thread-like molecules.

THE FINAL ADJUSTMENTS 129

built up from smaller molecules which are attached
to one another end to end. In this case the smaller
molecules are not nucleotides but are another variety
of chemical configuration known as amino acids. It
is natural to suppose that the sequence of nucleotides
along the thread of DNA in the chromosome deter-
mines a sequence of amino acids which will be built
together to form the protein produced by that gene.
This idea receives some confirmation when one looks
at the proteins produced by abnormal genes. Proteins
are such complicated substances that only in a few
cases have they been fully analysed. One case in which
the analysis has been carried very far is that of haemo-
globin, the red colouring matter of the blood. Certain
genes are known in man which produce abnormal
types of haemoglobin. It has been shown that several
of these abnormal haemoglobins differ from the nor-
mal one only by a change in a single amino acid, out
of the whole sequence of several hundred. This is just
what we should expect if the abnormality in the gene
was due, in the first place, to an alteration of one ol
its nucleotides, and this altered sequence of nucleo-
tides determined the appearance of an altered sequence
of amino acids.

We still do not know exactly how this sequence of
nucleotides in DNA determines the sequence of amino
acids in protein. It is certain that the process is not a
very simple one. For instance, the DNA is normally
found in the chromosomes inside the nucleus, and it is
doubtful if it ever moves far away from that location.

130 HOW ANIMALS DEVELOP

On the other hand, the proteins which are produced
under the influence of this DNA are not manufactured
in the nucleus, but in the cytoplasm. Evidence of this
has been gained largely by the use of radio isotopes.
One can synthesise in the laboratory an amino acid
which contains a radioactive atom, for instance, radio-
active carbon. This "labelled" amino acid can be put
into the medium surrounding a cell which is engaged
in manufacturing protein. After a time the cell can
be killed and sectioned and the sections covered with
a photographic emulsion. At any place at which the
labelled amino acid has been built into protein it will
continue to give off ionising radiations, which will pro-
duce a blackening in the photographic film above it.
In this way one can determine the sites at which the
protein is being produced. It turns out that only in the
earliest embryonic cells is the major site of protein
synthesis in the nucleus. In slightly later cells, which
are engaged in making the main proteins which will
build up, for instance, a muscle fibre or the substance
of a nerve cell, the labelled amino acids are incorpo-
rated into protein first in the cytoplasm. The actual
place at which they are formed can be located even
more precisely by other methods. If one grinds up a
cell and centrifuges it, first at low speed to remove the
larger debris, and then at higher and higher speeds,
one can isolate a series of fractions, each fraction con-
sisting of particles of roughly the same size. It turns
out that the fraction that contains the greater part of
the labelled amino acid consists of a group of very

THE FINAL ADJUSTMENTS 131

small granules known as microsomal particles. These
are too small to be individually visible with the light
microscope, but with the electron microscope they can
be seen as small dense granules lying in the cytoplasm.
They are often arranged on the surface of a number
of cytoplasmic membranes, which are referred to as the
ergastoplasm or endoplasmic reticulum.

It is clear that, if the genes in the nucleus are to
determine the sequence into which amino acids will be
built into proteins in the microsomal particles, there
must be some "messenger" which passes from gene to
particle, carrying, as it were, the blueprint for the pro-
tein. A great deal of research at the present day is
devoted to the problem of these messengers. There is
considerable evidence that the messenger is also a
nucleic acid, but one of a rather different type than that
in the chromosomes. The nucleotide building-blocks
of the hereditary DNA contain a sugar known as
deoxyribose, but cells also contain another type of
nucleic acid, in which the building-blocks have the
sugar ribose. The nucleic acid in which this is incor-
porated is known as RNA for short. It seems very
likely that the messenger passing from gene to micro-
somal particle is actually a kind of RNA, although it
also seems to be true that other types of RNA play
other roles in the cellular processes.

It will be seen from this account that we already
know a good deal about the processes by which genes
exert their influence during development. There are,
of course, still many details to be filled in, even in the

132 HOW ANIMALS DEVELOP

simple story of how one gene influences its correspond-
ing protein, and this is one of the most active fields of
present-day research. However, there is still another
problem, which is more difficult and in which we have
as yet made less progress. The developing cell is not
simply a bag in which a lot of quite separate processes
of protein synthesis are proceeding. On the contrary,
it is clear that the processes going on in it must be
co-ordinated in some way. A muscle cell produces, in
the right quantities, the various proteins that have to
be joined together to build up a functioning muscle
fibre. Similarly, in every other type of cell, there is a
fairly definite quantitative relation between the
amounts of the different proteins it contains. We have
very little idea how this integration of the processes
of synthesis is brought about. One hypothesis— though
perhaps at present it is little more than a guess— is
that the complex structural architecture which the
electron microscope is revealing has something to do
with this matter. It is certainly remarkable that now
that we can examine the interior of cells in much
greater detail than before, we keep on finding that
they possess elaborate systems of membranes and other
structures. These do not seem to be called for by the
simple story of protein synthesis described above, but
it is very difficult to believe that they have no function
at all. If we suppose that they operate in some way to
co-ordinate the processes of development, that does at
least provide them with a raison d'etre.

THE FINAL ADJUSTMENTS I33

Summing-up

This book started by considering the classical prob-
lems of embryology, with which biologists have been
concerned for centuries. We saw how the mere descrip-
tion of the patterns which are found led to the reca-
pitulation hypothesis and the discovery of the funda-
mental pattern of the three germ layers. We then saw
in outline how the elements of the pattern arise.
Processes go on in the egg which produce organ form-
ing substances, or evocators and competent tissues
which react to give determined organ rudiments.
These processes have two aspects. One is the "substance
aspect", which is concerned with the changes in the
nature of the substances by which the cells are com-
posed, which alters gradually as various regions of the
Ggg develop into cells of the nerves, muscles, kidneys,
liver, etc. The other is the "pattern aspect". Each cell
and organ of the body has a definite shape and struc-
tural organisation. The progress of understanding in
recent years has been in the main a digging down into
the basic processes underlying the substance aspect.
We have just seen in the last chapter how far we have
already got in understanding how hereditary genes
control the production of particular proteins. The
whole of the substance aspect of development can per-
haps be considered as an enormously elaborate and
complex composite made up out of elementary unit
processes of this kind. But a complete science can never

134 HOW ANIMALS DEVELOP

be built up wholly by digging downwards to the sim-
pler foundations. We must also build up, on whatever
foundations are available at the time, some system of
explanation for the more complex phenomena which
we see around us. We cannot claim to understand how
animals develop until we can explain how the various
individual processes of protein synthesis are integrated
with one another, and how the animal as a whole
comes to have a pattern and structure. Perhaps these
two problems are related. At any rate, we have to re-
member that they still face us with a lot of very diffi-
cult and fascinating questions. We know something
about how animals develop, but though our knowl-
edge is increasing all the time, we shall never know it
all. But then if we did know all about everything how
boring life would be.

INDEX

185

Activation centre, 75,

100
amphibia, 42 , 63, 84, 9 1 ,

103
animal pole, 27
armadillo, 87
ascidian, 83, 91
axial gradients, loi

Biogenetic law, 20
birds, 49, 70, 104
blastoderm, 50
blastopore, 23
blastula, 23
budding, loi
butterfly, 109

Cancer, 18, 116
caterpillar, 90
cell-division, 28
chick, 49, 70
chromosomes, 28
cinematography, 51, 81
cleavage, 36
closed-box eggs, 104
Communist party, 81
competence, 93, 100,

123
cultivation, 51, 58, 118
cytoplasm, 27

Determination, 62
developmental fate, 61
differentiation centre, 75
ductless glands, 1 15

Ectoderm, 24
egg, 26
cndoderm, 24
entelechy, 98
evocator, 85, 95, 116
evolution, 19
eye, 78, 80, 88, 1 1 1

Fertilization, 32
fish, 49
food, 102
frogs, 42, 91
function, 1 1 1

Gastrula, 23
gene, 32, 119, 122
germ cells, 24, 117
germ layers, 24
germ track, 1 1 7
gill slits, 20, 57
growth. 109

Harmonious equipo-
tential system, 80

hereditary factors, 32,
119, 122

hormones, 114

Immortality of germ

cells, 117
immortality, piecemeal,

individuation, 95
induction, 67
insects, 73, 90, 100, 109,
116

Joints, 87, III

Kidney, 82

Lamprey, 48
larva, 90, 1 1 6
leg, 80
lens, 79
localization, 86

Mammals, 54, 72, 105
man, 58, 86, 107
mendelism, 34
mesoderm, 24
microsurgery, 63
monstrosities, 59
mosaic eggs, 83
mutation, 32, 39

Nerves, 113
neural plate, 44
newts, 42, 63, 84
nucleus, 13, 16

Octopus, 88
organ - forming sub -
stances, 83, 118

organism, 14, 15
organizer, 18, 69, 70, 71,

72, 77, 96
orientation of particles,

112

Parthenogenesis, 35
phosphatase, 82
placenta, 55, 106
presumptive areas, 46,

48,53
primitive gut, 23, 41,

46, 69
primitive streak, 52, 55
protoplasm, 16

Recapitulation, 20
recapitulation,chcmical,

105
reduction division, 30
regeneration, 100
reptile, 49, 55, 104

Sea-urchins, 41, 72, 99
secondary organizers, 78
self-differentiation, 62,

79
sex, 106, 116, 121
size of eggs, etc., 26, 63
sorting yard, 96
sp>eed of development,

59
sperm, 26, 62

stain experiment, 43, 48,
51

Tadpoles, 1 1 1
turtle, 104
twins, 37, 86
tying-up experiment, 37

Uterine milk, 108

Vegetative pole, 27
virgin birth, 35

Wasps, 87

waste products, 104

Yolk, 16

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READINGS IN THE LITERATURE OF SCIENCE. Illustrated TB/512

ANIMAL ECOLOGY. Illustrated TB/543

THE MECHANISM OF EVOLUTION TB/5a7

C. V. Durell

Alexander Findlay

H. G. Forder

Werner Heisenberg

C. Judson Herrick

Max Jammer

J. E. Morton

O. Neugebauer

H. T. Pledge

O. W. Richards

Paul A. Schilpp, Ed.

P. M. Sheppard

L. S. Stebbing

A. G. Van Melsen

C. H. Waddington

G. J. Whitrow

TB/549

READABLE RELATIVITY TB/53O

CHEMISTRY IN THE SERVICE OF MAN. Illustrated TB/524

geometry: An Introduction. Illustrated TB/548

PHYSICS AND philosophy: The Revolution in Modern Science

the evolution of HUMAN NATURE TB/545
CONCEPTS OF FORCE TB/55O

molluscs: An Intro, to Their Form and Function. Ilhis. TB/529

THE EXACT SCIENCES IN ANTIQUITY TB/552

SCIENCE SINCE 1500: A Short History of Mathematics, Physics, Chemistry,

and Biology. Illustrated TB/506
THE SOCIAL INSECTS. Illustrated TB/542
ALBERT EINSTEIN: PhUosopher-Scientist. Vol.

NATURAL SELECTION AND HEREDITY. Illustrated
A MODERN INTRODUCTION TO LOGIC TB/538

FROM ATOMOS TO ATOM: The History of the Concept Atom
HOW ANIMALS DEVELOP. Illustrated TB/553 ■-♦

THE STRUCTURE AND EVOLUTION OF THE UNIVERSE: An Introduction to Cosmol-
ogy. Illustrated TB/504

/, TB/502; Vol. II, TB/503
TB/528

TB/517

HARPER TORCHBOOKS / The Cloister Library

Tor Andrae

Augustine/Przywara

C. K. Barrett, Ed.

Karl Barth

Anton T. Boisen

Martin Buber
Martin Buber

R. Bultmann
Jacob Burckhardt

Edward Conze

Frederick Copleston

H. G. Creel

Mircea Eliade

G. P. Fedotov

Henri Frankfort
Sigmund Freud

Edgar J. Goodspeed
Adolf Harnack

R. K. Harrison
Friedrich Hegel
Johan Huizinga
Flavius Josephus
Immanuel Kant
S0ren Kierkegaard
S0ren Kierkegaard

Alexandre Koyre

Walter Lowrie

A. C. McGiflFert

T. J. Meek

H. Richard Niebuhr

H. Richard Niebuhr

F. Schleiermacher

Teilhard de Chardin

Paul Tillich

E. B. Tylor

E. B. Tylor

Evelyn Underbill
Johannes Weiss

Wilhelm Windelband
Wilhelm Windelband

/
[Selected titles]

MOHAMMED: The Man and His Faith TB/62

AN AUGUSTINE SYNTHESIS TB/35

THE NEW TESTAMENT BACKGROUND: Selected Documents TB/86

DOGMATICS IN OUTLINE TB/56

THE EXPLORATION OF THE INNER WORLD; A Study of Meutol Disorder and
Religious Experience TB/87

MOSES : The Revelation and the Covenant TB/27

TWO TYPES OF FAITH: The Inter penetration of Judaism and Christianity
TB/75

HISTORY AND ESCHATOLOGY : The Presence of Eternity TB/91

THE CIVILIZATION OF THE RENAISSANCE IN ITALY. Illustrated Edition. Intro-
duction by B. Nelson and C. Trinkaus. Vol. I, TB/40; Vol. II, TB/41

buddhism: Its Essence and Development TB/58

MEDIEVAL philosophy TB/76

CONFUCIUS AND THE CHINESE WAY TB/63

THE SACRED AND THE PROFANE: The Significance of Religious Myth, Symbolism,
and Ritual within Life and Culture tb/8i

THE RUSSIAN RELIGIOUS MIND: Kiel an Christianity, the loth to the 13th
Centuries TB/70

ANCIENT EGYPTIAN RELIGION: An Interpretation. Illustrated TB/77

ON CREATIVITY AND THE UNCONSCIOUS: Papers on the Psychology of Art, Liter-
ature, Love, Religion. Edited by Benjamin Nelson TB/45

A LIFE OF JESUS TB/i

THE MISSION AND EXPANSION OF CHRISTIANITY IN THE FIRST THREE CENTURIES.

Introduction by Jaroslav Pelikan. TB/92
THE DEAD SEA SCROLLS: An Introduction TB/84
ON CHRISTIANITY: Early Theological Writings TB/79

ERASMUS AND THE AGE OF REFORMATION. Illustrated TB/19

THE GREAT ROMAN-JEWISH WAR, with The Life of Joscphus. tb/74

RELIGION WITHIN THE LIIIITS OF nE\SON ALONE TB/67

THE JOURNALS OF KIERKEGAARD: A Selection edited by A. Dru TB/52
THE POINT OF VIEW FOR MY WORK AS AN AUTHOR: A Report to History.
Foreword by Benjamin Nelson. tb/88

FROM THE CLOSED WORLD TO THE INFINITE UNIVERSE TB/31

KIERKEGAARD. Vol. I, TB/89; Vol. II, TB/90

PROTESTANT THOUGHT BEFORE KANT. Preface by J. Pelikan. TB/93

HEBREW ORIGINS TB/69

CHRIST AND CULTURE TB/3 *

THE KINGDOM OF GOD IN AMERICA TB/49

ON RELIGION: Speeches to Its Cultured Despisers. Intro, by R. Otto TB/36

THE PHENOMENON OF MAN TB/83

DYNAMICS OF FAITH TB/42

THE ORIGINS OF CULTURE [Part I of "Primitive Culture"]. Introduction by

Paul Radin TB/33
RELIGION IN PRIMITIVE CULTURE [Part II of "Primitive Culture"] Introduction

by Paul Radin TB/34
WORSHIP tb/io
EARLIEST CHRISTIANITY: A History of the Period ^.D. 30-150. Introduction

by F. C. Grant. Vol. I, TB/53; Vol. II, TB/54
A HISTORY OF PHILOSOPHY I: Greek, Roman, Medieval TB/38
A HISTORY OF PHILOSOPHY II: Renaissance, Enlightenment, Modern TB/39

C. H. WADDINGTON

How Animals Develop

A SHORT ACCOUNT OF THE SCIENCE OF EMBRYOLOGY

"The book may be confidently recommended to medical and scientific
students as well as to the general reader who wishes to obtain an
up-to-date survey of the modern science of experimental embryology.
It is the first book of its kind, at any rate in English, to present authori-
tatively in simple elementary language an outline of the way in which
animals develop and the causes which underlie the processes of
embryonic differentiation."— f. h. a. Marshall, Nature

''Mr. Waddington's book makes very good reading and gives a clear
though necessarily simplified, account of his subject ... For the student
this book will provide a stimulating introduction."— Lancet

"If one has some preliminary understanding of zoology and of scien-
tific methods, and an interest in the subject, Mr. Waddington's book
will provide some fascinated hours. And it has much value as an
account and summing up of the present status of embryology."—
The New York Times

HARPER & BROTHERS, NEW YORK

COVER DESIGN BY GUY FLEMING