#### TL;DR C.H. Waddington was the first biologist to say explic...
Conrad Hal Waddington was a British developmental biologist, geneti...
**Genotype:** The genotype of an organism is a description of that...
The term epigenetics is the study of how your behaviors and environ...
Waddington would later substitute the word epigenotype for the epig...
> ***"Thus genetics has to observe the phenotypes, the adult charac...
The species Drosophila melanogaster - often referred to as the frui...
> ***"Genes are not interlopers, which intrude from time to time to...
REPRINTS AND REFLECTIONS
The Epigenotype
C. H. Waddington*
The adult characteristics of animals, i.e. their phenotypes, must be studied in
order to reach conclusions about the genotypes, i.e. the hereditary constitutions
which form the basic subject-matter of genetics. But between genotype and
phenotype lies a whole complex of development processes, for which Dr
Waddington proposes the name ‘epigenotype.’ He here describes some of the
general characteristics of an epigenotype, with special reference to the fruit-fly
Drosophila melanogaster.
Of all the branches of biology it is genetics, the sci-
ence of heredity, which has been most successful in
finding a way of analysing an animal into represen-
tative units, so that its nature can be indicated by a
formula, as we represent a chemical compound by its
appropriate symbols. Genetics has been able to do this
because it studies animals in their simplest form,
namely as fertilized eggs, in which all the complexity
of the fully developed animal is implicit but not yet
present. But knowledge about the nature of the ferti-
lized egg is not derived directly from an examination
of eggs; it is deduced from a consideration of the
numbers and kinds of adults into which they develop.
Thus genetics has to observe the phenotypes, the adult
characteristics of animals, in order to reach conclu-
sions about the genotypes, the hereditary constitutions
which are its basic subject-matter.
For the purpose of a study of inheritance, the rela-
tion between phenotypes and genotypes can be left
comparatively uninvestigated; we need merely to
assume that changes in the genotype produce corre-
lated changes in the adult phenotype, but the mech-
anism of this correlation need not concern us. Yet this
question is, from a wider biological point of view, of
crucial importance, since it is the kernel of the whole
problem of development. Many geneticists have
recognized this and attempted to discover the pro-
cesses involved in the mechanism by which the
genes of the genotype bring about phenotypic effects.
The first step in such an enterprise is or rather
should be, since it is often omitted by those with an
undue respect for the powers of reason to describe
what can be seen of the developmental processes. For
enquiries of this kind, the word ‘phenogenetics was
coined by Haecker
1
. The second and more important
part of the task is to discover the causal mechanisms
at work, and to relate them as far as possible to what
experimental embryology has already revealed of the
mechanics of development. We might use the name
‘epigenetics’ for such studies, thus emphasizing their
relation to the concepts, so strongly favourable to the
classical theory of epigenesis, which have been
reached by the experimental embryologists. We cer-
tainly need to remember that between genotype and
phenotype, and connecting them to each other, there
lies a whole complex of developmental processes. It is
convenient to have a name for this complex: ‘epigen-
otype’ seems suitable
2
.
We know comparatively little about the general
characteristics of an epigenotype. One general feature,
however, is that it consists of concatenations of pro-
cesses linked together in a network, so that a disturb-
ance at an early stage may gradually cause more and
more far reaching abnormalities in many different
organs and tissues. Some very beautiful examples of
such effects have recently been described by
Gru¨neberg
3,4
based on mutations in his mouse
colony at University College, London. One gene, the
‘grey-lethal’, brings about a lack of yellow pigment in
the fur, and a failure of the absorption of bone which
normally accompanies growth. The latter effect entails
a whole host of secondary consequences. Thus the
minerals of the body are immobilized in the bones
and cannot be used for new growth, so that the
teeth are incompletely calcified and unable to masti-
cate solid food. Again, the lack of bone absorption
leads to pressure on some nerves, particularly those
serving the lower jaw; this presumably gives rise to
neuralgic pain, the animals are disinclined to take
even liquid nourishment, the starvation affects the
thymus gland, and the animals eventually die.
Another lethal gene, this time in the rat, brings
about even more manifold and at first sight uncon-
nected abnormalities. The first noticeable effect is an
abnormality in the development of cartilage, which
affects the ribs, and thus the lungs, circulatory
organs, and finally the growth rates of various parts.
* Waddington CH. The Epigenotpye. Endeavour 1942; 18–20
Reprinted with permission.
Published by Oxford University Press on behalf of the International Epidemiological Association
ß The Author 2011; all rights reserved. Advance Access publication 20 December 2011
International Journal of Epidemiology 2012;41:10–13
doi:10.1093/ije/dyr184
10
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