Once the future of a tissue's development is decided, it can behave in
a strikingly 'determined' way. At the gastrular stage, when the embryo
still looks like a partly infolded sac, it is nevertheless possible
already to tell which organs each region will produce. If at this early
stage a piece of tissue from an amphibian embryo, which would normally
give rise to an eye, is transplanted onto the tail end of another,
older embryo, it will become, not an eye, but a kidney-duct or some
other organ characteristic of that region. But at a later stage in the
embryo's growth, this docility of the presumptive eye-region is lost,
and no matter to what location it is transplanted, it will develop
into an eye -- even on the host's thigh or belly. When a cell-group has
reached this stage, it is called a morphogenetic field, organ-primordium,
or bud, as the case may be. Not only the future eye, but a limb-bud too,
transplanted to a different position (on the same, or on another embryo),
will form a complete organ; even a heart may be formed on the host's
flank. This 'ruthless' determination of morphogenetic fields to assert
their individuality reflects, in our terminology, the self-assertive
principle in development.
Each morphogenetic field or organ primordium displays the holistic
character of an automous unit, a self-regulating holon. If half of the
field's tissue is cut away, the remainder will form not half an organ but
a complete organ. If, at a certain stage of its development, the eye-cup
is split into several isolated parts, each fragment will form a smaller,
but normal, eye; and even the artificially scrambled and filtered cells
of a tissue will, as we have seen (
page 69
),
re-form again.
These autonomous, self-regulating properties of holons within the growing
embryo are a vital safeguard; they ensure that whatever accidental hazards
arise during development, the end-product will be according to norm. In
view of the millions and millions of cells which divide, differentiate,
and move about in the constantly changing environment of fluids and
neighbouring tissues -- Waddington called it 'the epigenetic landscape'
-- it must be assumed that no two embryos, not even identical twins,
are formed in exactly the same way. The self-regulating mechanisms
which correct deviations from the norm and guarantee, so to speak, the
end-result, have been compared to the homeostatic feedback devices in the
adult organism -- so biologists speak of 'developmental homeostasis'. The
future individual is potentially predetermined in the chromosomes of
the fertilised egg; but to translate this blueprint into the finished
product, billions of specialised cells have to be fabricated and moulded
into an integrated structure. The mind boggles at the idea that the genes
of that one fertilised egg should contain built-in provisions for each
and every particular contingency which every single one of its fifty-six
generations of daughter cells might encounter in the process. However,
the problem becomes a little less baffling if we replace the concept of
the 'genetic blueprint', which implies a plan to be rigidly copied, by
the concept of a genetic canon of rules which are fixed, but leave room
for alternative choices, i.e., flexible strategies guided by feedbacks
and pointers from the environment. But how can this formula be applied
to the development of the embryo?
The Genetic Keyboard
The cells of an embryo, all of identical origin, differentiate into such
diverse products as muscle cells, several varieties of blood cells,
a great variety of nerve cells, and so on, in spite of the fact that
each of them carries the same set of hereditary instructions in its
chromosomes. The activities of the cell, whether in embryo or adult, are
controlled by the genes located in the chromosomes.* But since we have
evidence that all cells in the body, whatever their function, contain the
same complete set of chromosomes, how can a nerve cell and a kidney cell
fulfil such different tasks, if they are governed by the same set of laws?
* To complicate matters, there also exist cytoplasmic carriers
of heredity, but for our present purpose these can be left out
of account.
A generation ago the answer to this question seemed to be simple. I shall
put it into a somewhat frivolous analogy. Let the chromosomes be represented
by the keyboard of a grand piano -- a very grand piano with thousands of
keys. Then each key will be a gene. Every cell in the body carries a
microscopic but complete keyboard in its nucleus. But each specialised
cell is only permitted to sound one chord, according to its speciality --
the rest of its genetic keyboard has been inactivated by scotch tape. The
fertilised egg, and the first few generations of its daughter cells, had
the complete keyboard at their disposal. But successive generations have,
at each 'point of no return', larger and larger areas of it covered by
scotch tape. In the end, a muscle cell can only do one thing: contract --
strike a single chord.
The scotch tape is known in the language of genetics as the 'repressor'.
The agent which strikes the key and activates the gene is an 'inducer'.
A mutated gene is a key which has gone out of tune. When quite a lot
of keys have gone quite a lot out of tune, the result, we were asked
to believe, was a much improved, wonderful new melody -- a reptile
transformed into a bird, or a monkey into a man. It seems that at some
point the theory must have gone wrong.
The point where it went wrong was the atomistic concept of the gene.
At the time when genetics got into its stride, atomism was in full bloom:
reflexes were atoms of behaviour, and genes were atomic units of heredity.
One gene was responsible for the colour of the eyes, a second for smooth
or kinky hair, a third for causing bleeding sickness; and the organism was
regarded as a collection of these mutually independent unit-characters
-- a mosaic of elementary bits, put together in the manner of Mekhos'
watches. But by the middle of our century, the rigidly atomistic concepts
of Mendelian genetics had become considerably softened up. It was realised
that a single gene may affect a wide rage of different characteristics
(pleiotropy); and vice versa, that a great number of genes may interact
to produce a single characteristic (polygeny). Some trivial characters --
like the colour of the eyes -- may depend on a single gene, but polygeny
is the rule, and the basic features of the orgasm depend on the totality
of genes -- the gene-complex or 'genome' as a whole.
In the early days of genetics, a gene could be 'dominant' or 'recessive',
and that was about all there was to it; but gradually more and more
terms had to be added to the vocabulary: repressors, apo-repressors,
co-repressors, inducers, modifier genes, switch genes, operator genes
which activate other genes, and even genes which regulate the rate of
mutations in genes. Thus the action of the gene-complex was originally
conceived as the unfolding of a simple linear sequence like that on a
tape-recorder or the Behaviourist's conditioned-reflex chain; whereas it
is now gradually becoming apparent that
the genetic controls operate as
a self-regulating micro-hierarchy
, equipped with feedback devices which
guide their flexible strategies.* This not only protects the growing
embryo against the hazards of ontogeny; it would also protect it against
the evolutionary hazards of phylogeny, or random mutations in its own
hereditary materials -- the blind antics of the monkey at the typewriter.
* Significantly, Waddington calls his important book on theoretical
biology The Strategy of the Genes (1957).
At the time of writing, this kind of suggestion still meets with
scepticism among the hard core of orthodox geneticists -- mainly, perhaps,
because its acceptance must lead to a decisive shift of emphasis in
our conception of the evolutionary process, as we shall see in the next
chapter. But atomism, at least, is on its way out; it is encouraging to
read, for instance, a passage like the following, quoted from a recent
textbook for college students:
All genes in the total inherited message tend to act together as an
integrated whole in the control of [embryonic] development. . . .
It is easy to fall into the habit of thinking that an organism
has a set number of characteristics with one gene controlling
each character. This is quite incorrect. The experimental
evidence indicates clearly that genes never work altogether
separately. Organisms are not patchworks with one gene controlling
each of the patches. They are integrated wholes, whose development
is controlled by the entire set of genes acting co-operatively. [3]
Since differentiation and morphogenesis proceed in hierarchic steps,
this co-operative activity of the gene-complex must also proceed in
a hierarchic order. The gene-complex is enclosed in the nucleus of
the cell. The nucleus is surrounded by the cell-body. The cell-body
is enclosed by a membrane, which is surrounded by body fluids and by
other cells, forming a tissue; this, in turn, is in contact with other
tissues. In other words, the gene complex operates in a
hierarchy of
environments
(page 102).
Different types of cells (brain cells, muscle cells, etc.) differ from
each other in the structure and chemistry of their cell-bodies. The
differences are due to the interaction between gene-complex, cell-body
and the cell's environment. In each growing and differentiating tissue a
different portion of the total gene-complex is active -- only that branch
of the gene-hierarchy which is concerned with the functions assigned to
the tissue in question; the remainder of the genes is 'switched off'. And
if we inquire into the nature of the agency which switches genes on and
off, we find once more the familiar devices of triggers and feedbacks. The
'triggers' are the chemical 'inducers', 'organisers', 'operators' and
'repressors', etc., already mentioned. Needless to say, the way they work
is only very imperfectly understood, and the proliferation of new terms is
sometimes just a convenient method to mask our ignorance of details. But
we know at least the broad principles involved. It is a process running
in circles -- in circles which get narrower, like the coils of a spiral,
as the cell becomes more and more specialised. The genes control the
activities of the cell by relatively simple coded instructions which are
spelt out in the complex operations of the cell-body. But the activities
of the genes are in turn guided by feedbacks from the cell-body, which
is exposed to the hierarchy of environments. This contains, apart from
chemical triggers, a number of other factors in the 'epigenetic landscape'
which are relevant to the cell's future, and about which the genes must
be informed. To use a term proposed by James Bonner [4], the cell must
be able to 'test' its neighbouts 'for strangeness or similarity, and in
many other ways'. By feeding back information on the lie of the land to
the gene-complex, the cytoplasm thus co-determines which genes should
be active and which should be temporarily or permanently switched off.
Thus ultimately a cell's fate depends on its position in the growing
embryo -- its exact location in the epigenetic landscape. Cells which
are members of the same morphogenetic field (for instance, a future arm)
must have the same genetic orchestration and behave like parts of a
coherent unit; and their further specialisation into 'solo players'
(individual fingers) will again depend on their position
within
the field. Each organ-bud is a Janus-faced holon: relative to its
earlier stages of development its destiny as a whole is irrevocably
determined; but relative to the future, its parts are still 'docile'
and will differentiate along the developmental pathway best suited to
their local environments. 'Determination' and 'docility', self-assertive
and integrative potential, are two sides of one medal (and so are, in
the terminology of a hoary controversy among biologists, 'regulative'
and 'mosaic' development).
In the types of hierarchies discussed before, the time factor played a
relatively subordinate part. In the developmental hierarchy, the apex
is the fertilised egg, the axis of the branching tree is the progress
of time, and the levels of the hierarchy are successive stages of
development. The structure of the growing embryo at any given moment is
a cross-section at right angles to the time axis, and the two faces of
Janus are turned towards the past and the future.
Summary
The purpose of this chapter was not to give a description of embryonic
development, but to point out the basic principles which this development
has in common with other forms of hierarchic processes discussed in
previous chapters. J. Needham once coined a phrase about 'the striving
of the blastula to grow into a chicken'. One might call the ensemble of
devices which make it succeed the organism's 'prenatal skills'. To quote
James Bonner again: 'We know that nature, like man, accomplishes complex
tasks by breaking them up into many simple sub-tasks.' [5] Development,
maturation, learning and acting are continuous processes, and we must
expect therefore that pre-natal and post-natal skills are governed by
the same general principles.
Some of these principles*, which we found reflected in embryonic
development, were: the hierarchically branching order of differentiation
and morphogenesis; the 'dissectibility' of that order into self-regulating
holons at various levels (stages); their Janus character (autonomy
versus dependence, determination versus docility); their fixed genetic
canons and adaptable strategies guided by feedbacks from the hierarchy
of environments; the action of triggers (inducers, etc.), which
release pre-set mechanisms, and of scanners ('tests') which process
information; the decrease of flexibility with increasing differentiation
and specialisation. Lastly, we found earlier on that the canon of fixed
rules which governs a skill is a 'hidden persuader', which operates
automatically or instinctively. Mutatis mutandis, we may say that an
analogous relation prevails between the genetic code of ancient origin
and the 'pre-natal skills' of the growing embryo.